1,4-cineole derivative and intermediate thereof, herbicide containing that derivative as active ingredient, method for using herbicide, and method for preparing agrochemical composition

Abstract

To provide a 1,4-cineole derivative, an intermediate thereof, a herbicide excellent in herbicidal activity and crop selectivity, etc.SOLUTION: The present invention provides a 1,4-cineole derivative represented by general formula (1), (1'), (2) or (2') that exhibits excellent herbicidal activity, an intermediate thereof, a herbicide characterized by containing the derivative as an active ingredient, etc. In general formulas (1), (1'), (2) and (2'), R1 to R3 and X each represent a specific substituent.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to 1,4-cineole derivatives and intermediates thereof, herbicides containing the derivatives as active ingredients and having extremely excellent control effects against harmful weeds in agricultural and horticultural cultivation settings or non-agricultural land, methods for using the herbicides, and methods for preparing pesticide compositions. [Background technology]

[0002] The use of herbicides is essential for protecting useful crops such as rice, wheat, corn, soybeans, cotton, and beets from weeds and increasing yields. In recent years, in cultivated fields where useful crops and weeds coexist, there has been a demand for selective herbicides that can selectively kill only weeds without causing phytotoxicity to crops. Furthermore, from the perspectives of preventing environmental pollution and reducing the economic costs of transportation and spraying, there is a need for herbicides that can exhibit high herbicidal effects at as low a dose as possible. Incidentally, 1,4-cineole derivatives exhibiting herbicidal activity similar to that of the present invention include those related to cinmethylin derivatives reported in Patent Document 1 and Non-Patent Document 1, but there are no compounds having a substituent at the C3 position of the bicyclo ring of the present invention. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] European Patent Publication No. 0081893 [Non-patent literature]

[0004] [Non-Patent Document 1] Journal of Agricultural and Food Chemistry, Vol. 58, 2010, pp. 10147-10155 Summary of the Invention [Problem to be solved by the invention]

[0005] An object of the present invention is to provide a 1,4-cineole derivative and an intermediate thereof, as well as a herbicide having excellent herbicidal activity and crop selectivity. Another object of the present invention is to provide a method for using the herbicide and a method for preparing the pesticide composition. [Means for solving the problem]

[0006] As a result of extensive research to solve the above problems, the present inventors have discovered that 1,4-cineole derivatives represented by the following general formula (1), (1'), (2) or (2') exhibit excellent herbicidal activity, and have completed the present invention.

[0007] That is, the present inventors have found that the above problems can be solved by the following configuration.

[0008] [1] A 1,4-cineole derivative represented by the following general formula (1), (1'), (2) or (2') (hereinafter, in this specification, this may be referred to as the "compound of the present invention").

[0009] [ka]

[0010] (In the general formulas (1), (1'), (2) and (2'), R 1are each independently a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkyl group (which may be mono- or poly-substituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), a C3-C6 cycloalkylC1-C6 alkyl group (which may be mono- or poly-substituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), a C1-C6 alkoxyC1-C6 alkyl group, a phenyl group (which may be mono- or poly-substituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), a heterocycle (which may be mono- or poly-substituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), a C7-C11 aralkyl group ... a heterocyclic C1-C6 alkyl group (which may be mono- or poly-substituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), a phenoxy C1-C6 alkyl group (which may be mono- or poly-substituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), a C7-C11 aralkyloxy C1-C6 alkyl group (which may be mono- or poly-substituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), or a benzoyl C1-C6 alkyl group (which may be mono- or poly-substituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups). R 2 and R 3each independently represents a hydrogen atom, a halogen atom, a hydroxyl group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 alkoxy-C1-C6 alkoxy group, a C1-C6 alkylcarbonyloxy group, a C1-C6 alkoxycarbonyloxy group, a C1-C6 alkylthiocarbonyloxy group, a C1-C6 alkylthiothiocarbonyloxy group, a C1-C6 alkylsulfonyloxy group, or a C1-C6 haloalkylsulfonyloxy group, and at least one of them is a substituent other than a hydrogen atom. 2 and R 3 two adjacent substituents, together with the carbons to which they are attached, form a 3- to 6-membered carbocyclic ring or a 3- to 6-membered heterocyclic ring having 1 to 4 heteroatoms independently selected from oxygen, sulfur, and nitrogen atoms, and the ring formed may have one or more substituents. X is an oxygen atom, a sulfur atom, or a CR 4 R 5 , or NR 6 Represents. R 4 and R 5 each independently represents a hydrogen atom or a C1-C6 alkyl group. R 6 is a hydrogen atom, a hydroxyl group, a C1-C6 alkyl group, a C1-C6 alkoxy group, an amino group, a C1-C6 alkylamino group, an aminocarbonylamino group, or a phenylamino group (which may be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group).

[0011] [2] R 1each independently represent a phenyl group (which may be mono- or poly-substituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), a C7-C11 aralkyl group (which may be mono- or poly-substituted with halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups), a heterocyclic C1-C6 alkyl group (which may be mono- or poly-substituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), a phenoxy C1-C6 alkyl group (which may be mono- or poly-substituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), or a benzoyl C1-C6 alkyl group (which may be mono- or poly-substituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups); R 2 and R 3 each independently represents a hydrogen atom, a halogen atom, a hydroxyl group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 alkoxyC1-C6 alkoxy group, a C1-C6 alkylthiothiocarbonyloxy group, or a C1-C6 haloalkylsulfonyloxy group, at least one of which is a substituent other than a hydrogen atom, and R 2 and R 3 two adjacent substituents, taken together with the carbons to which they are attached, form a 3- to 6-membered carbocyclic ring or a 3- to 6-membered heterocyclic ring having 1 to 4 heteroatoms independently selected from oxygen, sulfur and nitrogen atoms, wherein the ring formed optionally has one or more substituents; X is an oxygen atom, CR 4 R 5 , or NR 6 represents R 4 and R 5 each independently represents a hydrogen atom or a C1-C6 alkyl group, R 6represents a hydroxyl group, a C1-C6 alkyl group, a C1-C6 alkoxy group, an amino group, a C1-C6 alkylamino group, an aminocarbonylamino group, or a phenylamino group (which may be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group). The 1,4-cineole derivative according to [1].

[0012] [3] A synthetic intermediate represented by the following general formula (1a), (1a'), (2a) or (2a') (hereinafter, sometimes referred to as "intermediate of the present invention"), which is useful in producing the 1,4-cineole derivative represented by the general formula (1), (1'), (2) or (2') described in [1] or [2].

[0013] [ka]

[0014] (In the general formulas (1a), (1a'), (2a) and (2a'), R 1a each independently represents a hydrogen atom or a triC1-C6 alkylsilyl group, which may be the same or different. R 2a and R 3a each independently represents a hydrogen atom, a halogen atom, a hydroxyl group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 alkoxy-C1-C6 alkoxy group, a C1-C6 alkylcarbonyloxy group, a C1-C6 alkoxycarbonyloxy group, a C1-C6 alkylthiocarbonyloxy group, a C1-C6 alkylthiothiocarbonyloxy group, a C1-C6 alkylsulfonyloxy group, or a C1-C6 haloalkylsulfonyloxy group, and at least one of them is a substituent other than a hydrogen atom. 2a and R 3atwo adjacent substituents, together with the carbons to which they are attached, form a 3- to 6-membered carbocyclic ring or a 3- to 6-membered heterocyclic ring having 1 to 4 heteroatoms independently selected from oxygen, sulfur, and nitrogen atoms, and the ring formed may have one or more substituents. X a is an oxygen atom, a sulfur atom, and CR 4a R 5a , or NR 6a Represents. R 4a and R 5a each independently represents a hydrogen atom or a C1-C6 alkyl group. R 6a is a hydrogen atom, a hydroxyl group, a C1-C6 alkyl group, a C1-C6 alkoxy group, an amino group, a C1-C6 alkylamino group, an aminocarbonylamino group, or a phenylamino group (which may be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group).

[0015] [4] R 1a each independently represents a hydrogen atom or a tri-C1-C6 alkylsilyl group, which may be the same or different, R 2a and R 3a each independently represents a hydrogen atom, a halogen atom, a hydroxyl group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 alkoxyC1-C6 alkoxy group, a C1-C6 alkylthiothiocarbonyloxy group, or a C1-C6 haloalkylsulfonyloxy group, at least one of which is a substituent other than a hydrogen atom, and R 2a and R 3a two adjacent substituents, taken together with the carbons to which they are attached, form a 3- to 6-membered carbocyclic ring or a 3- to 6-membered heterocyclic ring having 1 to 4 heteroatoms independently selected from oxygen, sulfur and nitrogen atoms, wherein the ring formed optionally has one or more substituents; X a is an oxygen atom, CR 4a R 5a , or NR 6arepresents R 4a and R 5a each independently represents a hydrogen atom or a C1-C6 alkyl group, R 6a represents a hydroxyl group, a C1-C6 alkyl group, a C1-C6 alkoxy group, an amino group, a C1-C6 alkylamino group, an aminocarbonylamino group, or a phenylamino group (which may be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group). The synthetic intermediate according to [3].

[0016] [5] A herbicide containing the 1,4-cineole derivative according to [1] or [2] as an active ingredient. [6] The herbicide according to [5], which is for use on agricultural land, pasture, lawn, or non-agricultural land. [7] [5] The method for using the herbicide according to [5], wherein an effective amount of the 1,4-cineole derivative is applied to at least one selected from the foliage of weeds, soil, and water surface. [8] A method for preparing a pesticide composition, comprising the step of mixing the herbicide according to [5] with at least one selected from an extender and a surfactant. [Effects of the Invention]

[0017] According to the present invention, it is possible to provide 1,4-cineole derivatives and intermediates thereof, as well as herbicides having excellent herbicidal activity and crop selectivity. The novel 1,4-cineole derivatives of the present invention represented by the above general formula (1), (1'), (2) or (2') exhibit excellent herbicidal activity. The present invention also provides a method for using a herbicide and a method for preparing an agrochemical composition. DETAILED DESCRIPTION OF THE INVENTION

[0018] The 1,4-cineole derivatives related to the compounds of the present invention, the intermediates of the present invention, and herbicides containing the derivatives as active ingredients will now be described in detail.

[0019] In the 1,4-cineole derivative represented by the above general formula (1), (1′), (2) or (2′) of the present invention, and the synthetic intermediate represented by the above general formula (1a), (1a′), (2a) or (2a′), R 2 , R 3 , R 2a or R 3a Examples of the halogen atom or halogen atom as a substituent represented by the formula (I) include fluorine, chlorine, bromine, and iodine. The number of halogen atoms as a substituent may be one or more, and when there are two or more, the halogen atoms may be the same or different. The substitution position of the halogen atom may be any position.

[0020] R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 2a , R 3a , R 4a , R 5a , or R 6a Examples of the C1-C6 alkyl group represented by the formula (I) or as a substituent include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, an n-pentyl group, a neopentyl group, a 2-pentyl group, a 3-pentyl group, a tert-pentyl group, an n-hexyl group, an isohexyl group, a 2-hexyl group, and a 3-hexyl group. The number of C1-C6 alkyl groups as substituents may be one or more, and when there are two or more, the C1-C6 alkyl groups may be the same or different. The substitution position of the C1-C6 alkyl group may be any position.

[0021] R 1 , R 2 , R 3 , R 2a , or R 3aExamples of the C1-C6 haloalkyl group represented by the formula (I) or as a substituent include a monofluoromethyl group, a difluoromethyl group, a trifluoromethyl group, a 2,2,2-trifluoroethyl group, a 2-chloroethyl group, a trichloromethyl group, a 1-fluoroethyl group, a 2-fluoroethyl group, and a 6-fluorohexyl group.

[0022] R 1 Examples of the C2-C6 alkenyl group represented by the formula (I) include a vinyl group, a 1-propenyl group, a 2-propenyl group, a 1-butenyl group, a 2-butenyl group, a 3-butenyl group, a 1-methyl-2-propenyl group, a 2-methyl-2-propenyl group, a 1-pentenyl group, a 2-pentenyl group, a 3-pentenyl group, a 4-pentenyl group, a 1-methyl-2-butenyl group, a 2-methyl-2-butenyl group, a 1-hexenyl group, a 2-hexenyl group, a 3-hexenyl group, a 4-hexenyl group, and a 5-hexenyl group. R 1 Examples of the C2-C6 alkynyl group represented by the formula (I) include an ethynyl group, a 1-propynyl group, a propargyl group, a 1-butynyl group, a 2-butynyl group, a 3-butynyl group, a 1-methyl-2-propynyl group, a 2-methyl-3-butynyl group, a 1-pentynyl group, a 2-pentynyl group, a 3-pentynyl group, a 4-pentynyl group, a 1-methyl-2-butynyl group, a 2-methyl-3-pentynyl group, a 1-hexynyl group, and a 1,1-dimethyl-2-butynyl group.

[0023] R 1 Examples of the C3-C6 cycloalkyl group represented by the formula (I) include a cyclopropyl group, a 1-methylcyclopropyl group, a 2-methylcyclopropyl group, a 2,2-dimethylpropyl group, a cyclobutyl group, a cyclopentyl group, and a cyclohexyl group. R 1Examples of the C3-C6 cycloalkyl C1-C6 alkyl group represented by the formula (I) include a cyclopropylmethyl group, a cyclopropylethyl group, a 1-methylcyclopropylmethyl group, a 2-methylcyclopropylmethyl group, a 2,2-dimethylcyclopropylmethyl group, a cyclobutylmethyl group, a cyclopentylmethyl group, and a cyclohexylmethyl group.

[0024] R 1 Examples of the C1-C6 alkoxy C1-C6 alkyl group represented by the formula (I) include a methoxymethyl group, an ethoxymethyl group, an n-propoxymethyl group, an isopropoxymethyl group, an n-butoxymethyl group, a sec-butoxymethyl group, a tert-butoxymethyl group, a 1-pentyloxymethyl group, a 1-hexyloxymethyl group, a 2-methoxyethyl group, a 2-ethoxyethyl group, a 2-isopropoxyethyl group, a 2-isobutoxyethyl group, a 3-methoxypropyl group, a 2-methoxypropyl group, and a 2-methoxy-1-methylethyl group. R 1 Examples of the heterocycle represented by the formula (I) include a 2-pyridyl group, a 3-pyridyl group, a 4-pyridyl group, a 2-thienyl group, a 3-thienyl group, a 2-furfuryl group, a 3-furfuryl group, a 2-pyrimidyl group, a 4-pyrimidyl group, a 5-pyrimidyl group, a 6-pyrimidyl group, a 2-tetrahydrofurfuryl group, and a 3-tetrahydrofurfuryl group.

[0025] R 1 Examples of C7-C11 aralkyl groups represented by the formula (I) include benzyl, 1-phenethyl, 2-phenethyl, 1-phenylpropyl, 2-phenylpropyl, 3-phenylpropyl, 1-phenyl-2-methylpropyl, 1-phenylbutyl, and 1-phenylpentyl groups. R 1Examples of the heterocyclic C1-C6 alkyl group represented by the formula (I) include a 2-pyridylmethyl group, a 3-pyridylmethyl group, a 4-pyridylmethyl group, a 2-thienylmethyl group, a 3-thienylmethyl group, a 2-furfurylmethyl group, a 3-furfurylmethyl group, a 2-pyrimidylmethyl group, a 4-pyrimidylmethyl group, a 5-pyrimidylmethyl group, a 6-pyrimidylmethyl group, a 2-tetrahydrofurfuryl group, a 3-tetrahydrofurfuryl group, and the like.

[0026] R 1 Examples of the phenoxy C1-C6 alkyl group represented by the formula (I) include a 2-phenoxyethyl group, a 2-phenoxypropyl group, a 3-phenoxypropyl group, a 2-phenoxybutyl group, a 3-phenoxybutyl group, and a 4-phenoxybutyl group. R 1 Examples of the C7-C11 aralkyloxy C1-C6 alkyl group represented by the formula (I) include a benzyloxymethyl group, a 1-phenethyloxymethyl group, a 2-phenethyloxymethyl group, a 1-phenylpropoxymethyl group, a 2-phenylpropoxymethyl group, a 3-phenylpropoxymethyl group, and a benzyloxyethyl group. R 1 Examples of the benzoyl C1-C6 alkyl group represented by the formula (I) include a phenacyl group, a 1-phenyl-1-oxopropyl group, and a 1-phenyl-2-oxopropyl group.

[0027] R 2 , R 3 , R 6 , R 2a , R 3a , or R 6a Examples of the C1-C6 alkoxy group represented by the formula (I) or the C1-C6 alkoxy group as a substituent include a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a sec-butoxy group, and a tert-butoxy group. The number of C1-C6 alkoxy groups as substituents may be one or more, and when there are two or more, the C1-C6 alkoxy groups may be the same or different. In addition, the substitution position of the C1-C6 alkoxy group may be any position.

[0028] R 2 , R 3 , R 2a , or R 3a Examples of the C1-C6 alkoxy C1-C6 alkoxy group represented by the formula (I) include a methoxymethoxy group, an ethoxymethoxy group, an n-propoxymethoxy group, an isopropoxymethoxy group, an n-butoxymethoxy group, a sec-butoxymethoxy group, a tert-butoxymethoxy group, a 1-pentyloxymethoxy group, and a 1-hexyloxymethoxy group. R 2 , R 3 , R 2a , or R 3a Examples of the C1-C6 alkylcarbonyloxy group represented by the formula (I) include an acetyloxy group, an ethylcarbonyloxy group, an n-propylcarbonyloxy group, an isopropylcarbonyloxy group, an n-butylcarbonyloxy group, an isobutylcarbonyloxy group, a sec-butylcarbonyloxy group, a tert-butylcarbonyloxy group, a 1-pentylcarbonyloxy group, and a 1-hexylcarbonyloxy group.

[0029] R 2 , R 3 , R 2a , or R 3a Examples of the C1-C6 alkoxycarbonyloxy group represented by the formula (I) include a methoxycarbonyloxy group, an ethoxycarbonyloxy group, an n-propoxycarbonyloxy group, an isopropoxycarbonyloxy group, an n-butoxycarbonyloxy group, a sec-butoxycarbonyloxy group, and a tert-butoxycarbonyloxy group. R 2 , R 3 , R 2a , or R 3aExamples of the C1-C6 alkylthiocarbonyloxy group represented by the formula (I) include a methylthiocarbonyloxy group, an ethylthiocarbonyloxy group, an n-propylthiocarbonyloxy group, an isopropylthiocarbonyloxy group, an n-butylthiocarbonyloxy group, a sec-butylthiocarbonyloxy group, a tert-butylthiocarbonyloxy group, a 1-pentylthiocarbonyloxy group, and a 1-hexylthiocarbonyloxy group.

[0030] R 2 , R 3 , R 2a , or R 3a Examples of the C1-C6 alkylthiothiocarbonyloxy group represented by the formula (I) include a methylthiothiocarbonyloxy group, an ethylthiothiocarbonyloxy group, an n-propylthiothiocarbonyloxy group, an isopropylthiothiocarbonyloxy group, an n-butylthiothiocarbonyloxy group, a sec-butylthiothiocarbonyloxy group, a tert-butylthiothiocarbonyloxy group, a 1-pentylthiothiocarbonyloxy group, and a 1-hexylthiothiocarbonyloxy group. R 2 , R 3 , R 2a , or R 3a Examples of the C1-C6 alkylsulfonyloxy group represented by the formula (I) include a methanesulfonyloxy group, an ethanesulfonyloxy group, an n-propanesulfonyloxy group, an isopropanesulfonyloxy group, an n-butanesulfonyloxy group, an isobutanesulfonyloxy group, a sec-butanesulfonyloxy group, a tert-butanesulfonyloxy group, and an n-pentanesulfonyloxy group.

[0031] R 2 , R 3 , R 2a , or R 3aExamples of the C1-C6 haloalkylsulfonyloxy group represented by the formula (I) include a monofluoromethylsulfonyloxy group, a difluoromethylsulfonyloxy group, a trifluoromethylsulfonyloxy group, a monochloromethylsulfonyloxy group, a trichloromethylsulfonyloxy group, and a 2,2,2-trifluoroethylsulfonyloxy group. R 6 , or R 6a Examples of the C1-C6 alkylamino group represented by the formula (I) include a methylamino group, an ethylamino group, an n-propylamino group, an isopropylamino group, an n-butylamino group, an isobutylamino group, a sec-butylamino group, and a tert-butylamino group.

[0032] Examples of C1-C6 haloalkoxy groups as substituents include difluoromethoxy groups, trifluoromethoxy groups, 2,2,2-trifluoroethoxy groups, 2-chloroethylcarbonyl groups, trichloromethoxy groups, 1-fluoroethoxy groups, and 2-fluoroethoxy groups. R 1a Examples of the tri C1-C6 alkylsilyl group, which may be the same or different and is represented by the formula (I), include a trimethylsilyl group, a triethylsilyl group, a triisopropylsilyl group, a dimethylisopropylsilyl group, a diethylisopropylsilyl group, a dimethylhexylsilyl group, a tert-butyldimethylsilyl group, and a di-tert-butylmethylsilyl group.

[0033] In the 1,4-cineole derivative represented by the above general formula (1), (1'), (2) or (2'), R 1each independently represent a phenyl group (which may be mono- or poly-substituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), a C7-C11 aralkyl group (which may be mono- or poly-substituted with halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups), a heterocyclic C1-C6 alkyl group (which may be mono- or poly-substituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), a phenoxy C1-C6 alkyl group (which may be mono- or poly-substituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), or a benzoyl C1-C6 alkyl group (which may be mono- or poly-substituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups); R 2 and R 3 each independently represents a hydrogen atom, a halogen atom, a hydroxyl group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 alkoxyC1-C6 alkoxy group, a C1-C6 alkylthiothiocarbonyloxy group, or a C1-C6 haloalkylsulfonyloxy group, at least one of which is a substituent other than a hydrogen atom, and R 2 and R 3 two adjacent substituents, taken together with the carbons to which they are attached, form a 3- to 6-membered carbocyclic ring or a 3- to 6-membered heterocyclic ring having 1 to 4 heteroatoms independently selected from oxygen, sulfur and nitrogen atoms, wherein the ring formed optionally has one or more substituents; X is an oxygen atom, CR 4 R 5 , or NR 6 represents R 4 and R 5 each independently represents a hydrogen atom or a C1-C6 alkyl group, R 6represents a hydroxyl group, a C1-C6 alkyl group, a C1-C6 alkoxy group, an amino group, a C1-C6 alkylamino group, an aminocarbonylamino group, or a phenylamino group (which may be mono- or poly-substituted by halogen atoms, a C1-C6 alkyl group, or a C1-C6 haloalkyl group).

[0034] Furthermore, in the synthetic intermediate (intermediate of the present invention) represented by the general formula (1a), (1a'), (2a) or (2a') which is useful for producing the 1,4-cineole derivative represented by the general formula (1), (1'), (2) or (2'), R 1a each independently represents a hydrogen atom or a tri-C1-C6 alkylsilyl group, which may be the same or different, R 2a and R 3a each independently represents a hydrogen atom, a halogen atom, a hydroxyl group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 alkoxyC1-C6 alkoxy group, a C1-C6 alkylthiothiocarbonyloxy group, or a C1-C6 haloalkylsulfonyloxy group, at least one of which is a substituent other than a hydrogen atom, and R 2a and R 3a two adjacent substituents, taken together with the carbons to which they are attached, form a 3- to 6-membered carbocyclic ring or a 3- to 6-membered heterocyclic ring having 1 to 4 heteroatoms independently selected from oxygen, sulfur and nitrogen atoms, wherein the ring formed optionally has one or more substituents; X a is an oxygen atom, CR 4a R 5a , or NR 6a represents R 4a and R 5a each independently represents a hydrogen atom or a C1-C6 alkyl group, R 6arepresents a hydroxyl group, a C1-C6 alkyl group, a C1-C6 alkoxy group, an amino group, a C1-C6 alkylamino group, an aminocarbonylamino group, or a phenylamino group (which may be mono- or poly-substituted by halogen atoms, a C1-C6 alkyl group, or a C1-C6 haloalkyl group).

[0035] Representative examples of 1,4-cineole derivatives represented by general formula (1) or (1') are listed in Table 1 below, and representative examples of 1,4-cineole derivatives represented by general formula (2) or (2') are listed in Table 2 below, but the compounds are not limited to these. These compounds include optical isomers and compounds containing E- and Z-isomers. Compound numbers will be referenced in the following description.

[0036] The following symbols in the table represent the corresponding groups as follows: Furthermore, "H" represents a hydrogen atom, "Me" represents a methyl group, "Et" represents an ethyl group, "nPr" represents a normal propyl group, "iPr" represents an isopropyl group, "cPr" represents a cyclopropyl group, "nBu" represents a normal butyl group, "sBu" represents a sec-butyl group, "iBu" represents an isobutyl group, "tBu" represents a tert-butyl group, "cBu" represents a cyclobutyl group, "nPen" represents a normal pentyl group, "cPen" represents a cyclopentyl group, "nHex" represents a normal hexyl group, "cHex" represents a cyclohexyl group, "cHep" represents a cycloheptyl group, "cOct" represents a cyclooctyl group, "Ph" represents a phenyl group, and "Bz" represents a benzoyl group.

[0037] [Table 1]

[0038] [Table 2]

[0039] [Table 3]

[0040]

Table 4

[0041]

Table 5

[0042]

Table 6

[0043]

Table 7

[0044]

Table 8

[0045]

Table 9

[0046]

Table 10

[0047]

Table 11

[0048]

Table 12

[0049]

Table 13

[0050]

Table 14

[0051] [Table 15]

[0052] [Table 16]

[0053] [Table 17]

[0054] [Table 18]

[0055] Next, the method for producing the 1,4-cineole derivative represented by the above general formula (1), (1'), (2) or (2') of the present invention will be described in detail, but the method is not limited to these. Note that the reaction can be carried out using a magnetic stirrer, a mechanical stirrer, or a microwave synthesis device.

[0056] [Manufacturing method 1]

[0057] [ka]

[0058] Step 1 is a step of producing a diol derivative (4) by oxidizing α-terpinene represented by formula (3). α-Terpinene represented by formula (3) is known and can be obtained from Tokyo Chemical Industry Co., Ltd., etc. Examples of the oxidation method used in this step include a method using an oxidizing agent such as osmium tetroxide, potassium osmate, lead tetraacetate, potassium permanganate, sodium periodate and ruthenium chloride, or iodine and silver acetate, and oxidation in the presence of a reoxidizing agent such as potassium ferricyanide, N-methylmorpholine N-oxide, or tert-butyl hydroperoxide.

[0059] The reaction is preferably carried out in a solvent. Any solvent that is not harmful to the reaction can be used, including aromatic hydrocarbon solvents such as benzene, toluene, xylene, and chlorobenzene; aliphatic hydrocarbon solvents such as pentane, hexane, and octane; ether solvents such as diethyl ether, diisopropyl ether, cyclopentyl methyl ether, tetrahydrofuran, dimethoxyethane, and 1,4-dioxane; ketone solvents such as acetone, methyl ethyl ketone, and cyclohexanone; halogenated solvents such as chloroform and dichloromethane; nitrile solvents such as acetonitrile and propionitrile; ester solvents such as ethyl acetate, propyl acetate, butyl acetate, and methyl propionate; amide solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; alcohol solvents such as methanol, ethanol, 1-propanol, 2-propanol, and tert-butanol; dimethyl sulfoxide, water, hydrochloric acid, acetic acid, or a mixture thereof.

[0060] The reaction can be carried out at a temperature appropriately selected from the range of -20°C to 100°C, although this temperature varies depending on the oxidizing agent used and the reaction conditions. After completion of the reaction, the target product can be obtained by ordinary post-treatment procedures, but if necessary, it can also be purified by column chromatography, recrystallization, or the like. In this step, both isomers can be obtained individually by carrying out an asymmetric reaction using a chiral ligand such as (DHQ)2PHAL or (DHQD)2PHAL.

[0061] [Manufacturing method 2]

[0062] [ka]

[0063] (R 7 represents a C7-C11 aralkyl group (which may be mono- or poly-substituted with halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups), a heterocyclic C1-C6 alkyl group (which may be mono- or poly-substituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), or tri-C1-C6 alkylsilyl groups, which may be the same or different. Y represents a leaving group such as a halogen atom, methanesulfonyloxy group, trifluoromethanesulfonyloxy group, or toluenesulfonyloxy group.

[0064] Step-2 is a step of producing a monosubstituted compound (6) by reacting a diol derivative represented by formula (4) (hereinafter also referred to as substrate (4) or diol (4)) with a compound represented by formula (5) (hereinafter also referred to as substrate (5)) in the presence of a base. This reaction may be carried out in the presence of a base, and examples of the base that can be used include organic bases such as triethylamine, diisopropylethylamine, tributylamine, propylamine, butylamine, tert-butylamine, benzylamine, N-methylmorpholine, N,N-dimethylaniline, N,N-diethylaniline, 4-tert-butyl-N,N-dimethylaniline, pyridine, 4-dimethylaminopyridine, picoline, lutidine, pyrazine, imidazole, and N-methylimidazole; and alkali metal salts such as sodium carbonate, potassium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate, sodium acetate, potassium acetate, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydride, potassium hydride, sodium amide, butyllithium, tert-butyllithium, sec-butyllithium, lithium diisopropylamide, trimethylsilyllithium, lithium hexamethyldisilazide, sodium hexamethyldisilazide, and potassium hexamethyldisilazide. The target product can be obtained in good yield by using 0.1 to 5 equivalents of the base relative to the substrate. The reactant (5) is usually used in an amount of 1 to 5 equivalents relative to the substrate (4).

[0065] The reaction is preferably carried out in a solvent. Any solvent that is not harmful to the reaction can be used, including aromatic hydrocarbon solvents such as benzene, toluene, xylene, and chlorobenzene; aliphatic hydrocarbon solvents such as pentane, hexane, and octane; ether solvents such as diethyl ether, diisopropyl ether, cyclopentyl methyl ether, tetrahydrofuran, dimethoxyethane, and 1,4-dioxane; ketone solvents such as acetone, methyl ethyl ketone, and cyclohexanone; halogenated solvents such as chloroform and dichloromethane; nitrile solvents such as acetonitrile and propionitrile; ester solvents such as ethyl acetate, propyl acetate, butyl acetate, and methyl propionate; amide solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; alcohol solvents such as methanol, ethanol, 1-propanol, 2-propanol, and tert-butanol; dimethyl sulfoxide; water; and mixtures thereof.

[0066] The reaction can be carried out at a temperature appropriately selected from the range of -90°C to 200°C, although this temperature varies depending on the base used and the reaction conditions. After completion of the reaction, the target product can be obtained by ordinary post-treatment procedures, but if necessary, it can also be purified by column chromatography, recrystallization, or the like. In this step, by using 1S,2R-(4) and 1R,2S-(4) instead of diol (4), both isomers can be obtained while retaining their stereochemistry.

[0067] [Manufacturing method 3] [ka]

[0068] (R 7 has the same meaning as above.) Step 3 is a step of producing an epoxy derivative (7) by oxidizing the olefin derivative represented by formula (6). The obtained epoxy derivative (7) is a mixture of 1R,6R-(7) and 1S,6S-(7), and can be easily separated and purified by column chromatography or the like. Examples of oxidizing agents that can be used in this reaction include peroxides such as hydrogen peroxide, m-chloroperbenzoic acid, peracetic acid, tert-butyl hydroperoxide, sodium periodate, and OXONE (trade name of E.I. DuPont; containing potassium hydrogen peroxosulfate), N-chlorosuccinimide, N-bromosuccinimide, tert-butyl dichlorite, sodium hypochlorite, and oxygen. The desired product can be obtained in good yield by using 0.1 to 10 equivalents of the oxidizing agent relative to the substrate.

[0069] The reaction is preferably carried out in a solvent, and any solvent that is not harmful to the reaction can be used, including aromatic hydrocarbon solvents such as benzene, toluene, xylene, and chlorobenzene, aliphatic hydrocarbon solvents such as pentane, hexane, and octane, ether solvents such as diethyl ether, diisopropyl ether, cyclopentyl methyl ether, tetrahydrofuran, dimethoxyethane, and 1,4-dioxane, ketone solvents such as acetone, methyl ethyl ketone, and cyclohexanone, halogenated solvents such as chloroform and dichloromethane, water, and mixtures thereof. The reaction can be carried out at a temperature appropriately selected from the range of -90°C to 200°C, although this temperature varies depending on the oxidizing agent used and the reaction conditions. After completion of the reaction, the target product can be obtained by ordinary post-treatment procedures, but if necessary, it can also be purified by column chromatography, recrystallization, or the like. In this step, both isomers of olefin derivatives (6) can be obtained by carrying out the asymmetric reaction in step-1, using 1S,2R-(4) and 1R,2S-(4) as starting materials in step-2, instead of olefin derivative (6), while maintaining the stereochemistry.

[0070] [Manufacturing method 4]

[0071] [ka]

[0072] (R 7 has the same meaning as above.) Step 4 is a step of producing a 1,4-cineole derivative (8) by ring-opening the epoxy derivative represented by formula (7) using an acid and simultaneously carrying out intramolecular cyclization. Acids that can be used in this reaction include organic and inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, acetic acid, trifluoroacetic acid, p-tosylic acid, pyridinium p-toluenesulfonate, methanesulfonic acid, trifluoromethanesulfonic acid, camphorsulfonic acid, benzenesulfonic acid, fluorosulfonic acid, chloric acid, bromic acid, iodic acid, perbromic acid, thiocyanic acid, metaperiodic acid, hexafluorophosphoric acid, tetrafluoroboric acid, chlorobenzoic acid, and fluorobenzoic acid. The target product can be obtained in good yield by using 0.1 to 5 equivalents of acid relative to the substrate.

[0073] The reaction is preferably carried out in a solvent. Any solvent that is not harmful to the reaction can be used, including aromatic hydrocarbon solvents such as benzene, toluene, xylene, and chlorobenzene; aliphatic hydrocarbon solvents such as pentane, hexane, and octane; ether solvents such as diethyl ether, diisopropyl ether, cyclopentyl methyl ether, tetrahydrofuran, dimethoxyethane, and 1,4-dioxane; ketone solvents such as acetone, methyl ethyl ketone, and cyclohexanone; halogenated solvents such as chloroform and dichloromethane; nitrile solvents such as acetonitrile and propionitrile; ester solvents such as ethyl acetate, propyl acetate, butyl acetate, and methyl propionate; amide solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; alcohol solvents such as methanol, ethanol, 1-propanol, 2-propanol, and tert-butanol; dimethyl sulfoxide, water, hydrochloric acid, acetic acid, or a mixture thereof.

[0074] The reaction can be carried out at a temperature appropriately selected from the range of -90°C to 200°C, although this temperature varies depending on the acid used and the reaction conditions. After completion of the reaction, the target product can be obtained by ordinary post-treatment procedures, but if necessary, it can also be purified by column chromatography, recrystallization, or the like. In this step, instead of the epoxy derivative (7), 1S,2R-(4) and 1R,2S-(4) obtained by the asymmetric reaction in step-1 are used as starting materials to carry out steps-2 and -3 to obtain the respective isomers of epoxy derivative (7), whereby each isomer can be obtained while retaining its stereochemistry.

[0075] [Manufacturing method 5]

[0076] [ka]

[0077] (R 7 has the same meaning as above.) Step 5 is a step of producing a ketone derivative (9) by oxidizing a 1,4-cineole derivative represented by formula (8).

[0078] The oxidation reactions used in this reaction include Swern oxidation using dimethyl sulfoxide, oxalyl chloride, and triethylamine, PCC oxidation and PDC oxidation using pyridinium chlorochromate or pyridinium dichromate, oxidation using Dess-Martin periodinane or 2-iodoxybenzoic acid (IBX), TPAP oxidation using tetrapropylammonium perruthenate, and oxidation using 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO) or 2-azaadatomyl. Oxidation using nitroxy radicals such as 2-hydroxy-2-azaadamantane (AZADOL), iodobenzene diacetate (PIDA), 1-acetoxy-1,2-benziodoxol-3(1H)-one (ABX), or 1-(tert-butylperoxy)-1,2-benziodoxol-3-one, or N-tert-butylbenzenesulfinimidoyl chloride can be used. The desired product can be obtained in good yield by using 0.1 to 10 equivalents of the oxidizing agent relative to the substrate.

[0079] The reaction is preferably carried out in a solvent, and any solvent that is not harmful to the reaction can be used, including aromatic hydrocarbon solvents such as benzene, toluene, xylene, and chlorobenzene, aliphatic hydrocarbon solvents such as pentane, hexane, and octane, ether solvents such as diethyl ether, diisopropyl ether, cyclopentyl methyl ether, tetrahydrofuran, dimethoxyethane, and 1,4-dioxane, ketone solvents such as acetone, methyl ethyl ketone, and cyclohexanone, halogenated solvents such as chloroform and dichloromethane, water, and mixtures thereof. The reaction can be carried out at a temperature appropriately selected from the range of -90°C to 200°C, although this temperature varies depending on the oxidizing agent used and the reaction conditions. After completion of the reaction, the target product can be obtained by ordinary post-treatment procedures, but if necessary, it can also be purified by column chromatography, recrystallization, or the like. In this step, instead of the 1,4-cineole derivative (8), 1S,2R-(4) and 1R,2S-(4) obtained by the asymmetric reaction in step-1 are used as starting materials to carry out steps-2, -3, and -4 to obtain the isomeric 1,4-cineole derivative (8), whereby each isomer can be obtained while retaining its stereochemistry.

[0080] [Manufacturing method 6]

[0081] [ka]

[0082] (R 4 , R 5 and R 7 has the same meaning as above.) Step 6 is a step of producing an olefin derivative (10) by subjecting a ketone derivative represented by formula (9) to a Wittig reaction with a phosphonium ylide.

[0083] This reaction may be carried out in the presence of a base, and examples of the base that can be used include alkali metal salts such as sodium carbonate, potassium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate, sodium acetate, potassium acetate, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydride, potassium hydride, sodium amide, butyllithium, tert-butyllithium, sec-butyllithium, lithium diisopropylamide, trimethylsilyllithium, sodium hexamethyldisilazide, potassium hexamethyldisilazide, and lithium hexamethyldisilazide.

[0084] The reaction is preferably carried out in a solvent. Any solvent that is not harmful to the reaction can be used, including aromatic hydrocarbon solvents such as benzene, toluene, xylene, and chlorobenzene; aliphatic hydrocarbon solvents such as pentane, hexane, and octane; ether solvents such as diethyl ether, diisopropyl ether, cyclopentyl methyl ether, tetrahydrofuran, dimethoxyethane, and 1,4-dioxane; halogenated solvents such as chloroform and dichloromethane; nitrile solvents such as acetonitrile and propionitrile; ester solvents such as ethyl acetate, propyl acetate, butyl acetate, and methyl propionate; amide solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; alcohol solvents such as methanol, ethanol, 1-propanol, 2-propanol, and tert-butanol; dimethyl sulfoxide; water; and mixtures thereof.

[0085] The reaction can be carried out at a temperature appropriately selected from the range of -90°C to 200°C, although this temperature varies depending on the base used and the reaction conditions. After completion of the reaction, the target product can be obtained by ordinary post-treatment procedures, but if necessary, it can also be purified by column chromatography, recrystallization, or the like. In this step, instead of the ketone derivative (9), 1S,2R-(4) and 1R,2S-(4) obtained by the asymmetric reaction in step-1 are used as starting materials to carry out steps-2, -3, -4, and -5 to obtain the respective isomers of the ketone derivative (9), thereby allowing the respective isomers to be obtained while retaining their stereochemistry.

[0086] [Manufacturing method 7]

[0087] [ka]

[0088] (R 7 has the same meaning as above. 8represents a C1-C6 alkyl group or a C1-C6 haloalkyl group. Z represents a halogen atom. Step-7 is a step of producing a 1,4-cineole derivative (13) by reacting a ketone derivative represented by formula (9) with an organometallic compound represented by formula (11) or formula (12).

[0089] The reaction is preferably carried out in a solvent, and any solvent that is not harmful to the reaction can be used, including aromatic hydrocarbon solvents such as benzene, toluene, xylene, and chlorobenzene, aliphatic hydrocarbon solvents such as pentane, hexane, and octane, ether solvents such as diethyl ether, diisopropyl ether, cyclopentyl methyl ether, tetrahydrofuran, dimethoxyethane, and 1,4-dioxane, ketone solvents such as acetone, methyl ethyl ketone, and cyclohexanone, halogenated solvents such as chloroform and dichloromethane, and mixtures thereof. The reaction can be carried out at a temperature appropriately selected from the range of -90°C to 200°C, although this temperature varies depending on the reaction conditions. After completion of the reaction, the target product can be obtained by ordinary post-treatment procedures, but if necessary, it can also be purified by column chromatography, recrystallization, or the like. In this step, instead of the ketone derivative (9), 1S,2R-(4) and 1R,2S-(4) obtained by the asymmetric reaction in step-1 are used as starting materials to carry out steps-2, -3, -4, and -5 to obtain the respective isomers of the ketone derivative (9), thereby allowing the respective isomers to be obtained while retaining their stereochemistry.

[0090] [Manufacturing method 8]

[0091] [ka]

[0092] (R 6 , R 7 represents the same meaning as above.) Step-8 is a step of producing an imine derivative (15) by reacting a ketone derivative represented by formula (9) with an amine compound represented by formula (14). The amine compound (14) used in this reaction can also be used as a salt, and examples of the salt include hydrochloride, sulfate, carbonate, and the like.

[0093] This reaction may be carried out in the presence of an acid or a base. Examples of the acid that can be used include hydrochloric acid, sulfuric acid, and acetic acid. Examples of the base that can be used include organic bases such as triethylamine, diisopropylethylamine, tributylamine, propylamine, butylamine, tert-butylamine, benzylamine, N-methylmorpholine, N,N-dimethylaniline, N,N-diethylaniline, 4-tert-butyl-N,N-dimethylaniline, pyridine, 4-dimethylaminopyridine, picoline, lutidine, pyrazine, imidazole, and N-methylimidazole; and alkali metal salts such as sodium carbonate, potassium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate, sodium acetate, potassium acetate, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydride, potassium hydride, sodium amide, butyllithium, tert-butyllithium, lithium diisopropylamide, trimethylsilyllithium, and lithium hexamethyldisilazide. The target product can be obtained in good yield by using 0.1 to 10 equivalents of an acid or base relative to the substrate in the reaction.

[0094] The reaction is preferably carried out in a solvent. Any solvent that is not harmful to the reaction can be used, including aromatic hydrocarbon solvents such as benzene, toluene, xylene, and chlorobenzene; aliphatic hydrocarbon solvents such as pentane, hexane, and octane; ether solvents such as diethyl ether, diisopropyl ether, cyclopentyl methyl ether, tetrahydrofuran, dimethoxyethane, and 1,4-dioxane; halogenated solvents such as chloroform and dichloromethane; nitrile solvents such as acetonitrile and propionitrile; ester solvents such as ethyl acetate, propyl acetate, butyl acetate, and methyl propionate; amide solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; alcohol solvents such as methanol, ethanol, 1-propanol, 2-propanol, and tert-butanol; dimethyl sulfoxide; water; and mixtures thereof. The reaction can be carried out at a temperature appropriately selected from the range of 0°C to 200°C, although this temperature varies depending on the base used and the reaction conditions. After completion of the reaction, the target product can be obtained by ordinary post-treatment procedures, but if necessary, it can also be purified by column chromatography, recrystallization, or the like. In this step, instead of the ketone derivative (9), 1S,2R-(4) and 1R,2S-(4) obtained by the asymmetric reaction in step-1 are used as starting materials to carry out steps-2, -3, -4, and -5 to obtain the respective isomers of the ketone derivative (9), thereby allowing the respective isomers to be obtained while retaining their stereochemistry.

[0095] [Manufacturing method 9]

[0096] [ka]

[0097] (R 7 , Y has the same meaning as above. 9represents a C1-C6 alkyl group, a C1-C6 alkoxyC1-C6 alkyl group, a C1-C6 alkylcarbonyl group, a C1-C6 alkoxycarbonyl group, a C1-C6 alkylthiocarbonyl group, a C1-C6 alkylthiothiocarbonyl group, a C1-C6 alkylsulfonyl group, or a C1-C6 haloalkylsulfonyl group. Step 9 is a step of producing a 1,4-cineole derivative (17) by reacting a compound represented by formula (16) with the 3-hydroxyl group of a 1,4-cineole derivative represented by formula (8).

[0098] This reaction may be carried out in the presence of a base, and examples of the base that can be used include organic bases such as triethylamine, diisopropylethylamine, tributylamine, propylamine, butylamine, tert-butylamine, benzylamine, N-methylmorpholine, N,N-dimethylaniline, N,N-diethylaniline, 4-tert-butyl-N,N-dimethylaniline, pyridine, 4-dimethylaminopyridine, picoline, lutidine, pyrazine, imidazole, and N-methylimidazole; and alkali metal salts such as sodium carbonate, potassium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate, sodium acetate, potassium acetate, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydride, potassium hydride, sodium amide, butyllithium, tert-butyllithium, sec-butyllithium, lithium diisopropylamide, trimethylsilyllithium, sodium hexamethyldisilazide, potassium hexamethyldisilazide, and lithium hexamethyldisilazide. The target product can be obtained in good yield by using 0.1 to 10 equivalents of the base relative to the substrate in the reaction.

[0099] The solvent used in this reaction can be any solvent that is not harmful to the reaction, and examples thereof include aromatic hydrocarbon solvents such as benzene, toluene, xylene, and chlorobenzene; aliphatic hydrocarbon solvents such as pentane, hexane, and octane; ether solvents such as diethyl ether, diisopropyl ether, cyclopentyl methyl ether, tetrahydrofuran, dimethoxyethane, and 1,4-dioxane; ketone solvents such as acetone, methyl ethyl ketone, and cyclohexanone; halogenated solvents such as chloroform and dichloromethane; nitrile solvents such as acetonitrile and propionitrile; ester solvents such as ethyl acetate, propyl acetate, butyl acetate, and methyl propionate; amide solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; alcohol solvents such as methanol, ethanol, 1-propanol, 2-propanol, and tert-butanol; dimethyl sulfoxide; water; and mixtures thereof. The reaction can be carried out at a temperature appropriately selected from the range of 0°C to 200°C, although this temperature varies depending on the base used and the reaction conditions. After completion of the reaction, the target product can be obtained by ordinary post-treatment procedures, but if necessary, it can also be purified by column chromatography, recrystallization, or the like. In this step, instead of the 1,4-cineole derivative (8), 1S,2R-(4) and 1R,2S-(4) obtained by the asymmetric reaction in step-1 are used as starting materials to carry out steps-2, -3, and -4 to obtain the isomeric 1,4-cineole derivative (8), whereby each isomer can be obtained while retaining its stereochemistry.

[0100] [Manufacturing method 10]

[0101] [ka]

[0102] (R 7 represents the same meaning as above.) Step 10 is a step of reacting a 1,4-cineole derivative represented by formula (8) with ethyl vinyl ether (18) in the presence of an acid catalyst to produce an ether derivative represented by formula (19). The acid used as a catalyst in this reaction can be an organic or inorganic acid such as hydrochloric acid, sulfuric acid, acetic acid, p-tosylic acid, pyridinium p-toluenesulfonate, etc. The target product can be obtained in good yield by using 0.001 to 1 equivalent of the acid relative to the substrate.

[0103] The reaction is preferably carried out in a solvent. Any solvent that is not harmful to the reaction can be used, including aromatic hydrocarbon solvents such as benzene, toluene, xylene, and chlorobenzene; aliphatic hydrocarbon solvents such as pentane, hexane, and octane; ether solvents such as diethyl ether, diisopropyl ether, cyclopentyl methyl ether, tetrahydrofuran, dimethoxyethane, and 1,4-dioxane; ketone solvents such as acetone, methyl ethyl ketone, and cyclohexanone; halogenated solvents such as chloroform and dichloromethane; nitrile solvents such as acetonitrile and propionitrile; ester solvents such as ethyl acetate, propyl acetate, butyl acetate, and methyl propionate; amide solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; alcohol solvents such as methanol, ethanol, 1-propanol, 2-propanol, and tert-butanol; dimethyl sulfoxide; water; and mixtures thereof.

[0104] The reaction can be carried out at a temperature appropriately selected from the range of 0°C to 200°C, although this temperature varies depending on the acid used and the reaction conditions. After completion of the reaction, the target product can be obtained by ordinary post-treatment procedures, but if necessary, it can also be purified by column chromatography, recrystallization, or the like. In this step, instead of the 1,4-cineole derivative (8), 1S,2R-(4) and 1R,2S-(4) obtained by the asymmetric reaction in step-1 are used as starting materials to carry out steps-2, -3, and -4 to obtain the isomeric 1,4-cineole derivative (8), whereby each isomer can be obtained while retaining its stereochemistry.

[0105] [Manufacturing method 11]

[0106] [ka]

[0107] (R 2a , R 3b has the same meaning as above. 10 represent tri C1-C6 alkylsilyl groups, which may be the same or different. Step-11 is a step of producing a 1,4-cineole derivative represented by formula (21) by deprotecting the silyl ether derivative represented by formula (20) in the presence of an acid or fluoride ion. The acid used in this reaction may be an organic or inorganic acid such as hydrochloric acid, sulfuric acid, nitric acid, acetic acid, trifluoroacetic acid, p-tosylic acid, pyridinium p-toluenesulfonate, methanesulfonic acid, trifluoromethanesulfonic acid, camphorsulfonic acid, benzenesulfonic acid, fluorosulfonic acid, chloric acid, bromic acid, iodic acid, perbromic acid, thiocyanic acid, metaperiodic acid, hexafluorophosphoric acid, tetrafluoroboric acid, chlorobenzoic acid, or fluorobenzoic acid. The target product can be obtained in good yield by using 0.1 to 10 equivalents of the acid relative to the substrate. The fluoride ions used in this reaction include potassium fluoride, cesium fluoride, hydrofluoric acid and its salts, tetrabutylammonium fluoride, etc. The target product can be obtained in good yield by using 0.1 to 10 equivalents of fluoride ions relative to the substrate.

[0108] The reaction is preferably carried out in a solvent. Any solvent that is not harmful to the reaction can be used, including aromatic hydrocarbon solvents such as benzene, toluene, xylene, and chlorobenzene; aliphatic hydrocarbon solvents such as pentane, hexane, and octane; ether solvents such as diethyl ether, diisopropyl ether, cyclopentyl methyl ether, tetrahydrofuran, dimethoxyethane, and 1,4-dioxane; ketone solvents such as acetone, methyl ethyl ketone, and cyclohexanone; halogenated solvents such as chloroform and dichloromethane; nitrile solvents such as acetonitrile and propionitrile; ester solvents such as ethyl acetate, propyl acetate, butyl acetate, and methyl propionate; amide solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; alcohol solvents such as methanol, ethanol, 1-propanol, 2-propanol, and tert-butanol; dimethyl sulfoxide; water; and mixtures thereof.

[0109] The reaction can be carried out at a temperature appropriately selected from the range of 0°C to 200°C, although this temperature varies depending on the acid used and the reaction conditions. After completion of the reaction, the target product can be obtained by ordinary post-treatment procedures, but if necessary, it can also be purified by column chromatography, recrystallization, or the like. In this step, instead of the silyl ether derivative (20), 1S,2R-(4) and 1R,2S-(4) obtained by the asymmetric reaction in step-1 are used as starting materials, and steps-2, -3, -4, -5 and -7, or steps-2, -3, -4, -5 and -9, or steps-2, -3, -4, -5 and -10 are carried out to obtain each isomer of the silyl ether derivative (20), while maintaining its stereochemistry.

[0110] [Manufacturing method 12]

[0111] [ka]

[0112] (X a , R 10 represents the same meaning as above.) Step-12 is a step of producing a 1,4-cineole derivative represented by formula (23) by deprotecting the silyl ether derivative represented by formula (22) in the presence of an acid or fluoride ion. The acid used in this reaction may be an organic or inorganic acid such as hydrochloric acid, sulfuric acid, nitric acid, acetic acid, trifluoroacetic acid, p-tosylic acid, pyridinium p-toluenesulfonate, methanesulfonic acid, trifluoromethanesulfonic acid, camphorsulfonic acid, benzenesulfonic acid, fluorosulfonic acid, chloric acid, bromic acid, iodic acid, perbromic acid, thiocyanic acid, metaperiodic acid, hexafluorophosphoric acid, tetrafluoroboric acid, chlorobenzoic acid, or fluorobenzoic acid. The target product can be obtained in good yield by using 0.1 to 10 equivalents of the acid relative to the substrate. The fluoride ions used in this reaction include sodium fluoride, potassium fluoride, cesium fluoride, hydrofluoric acid and its salts, tetrabutylammonium fluoride, etc. The target product can be obtained in good yield by using 0.1 to 10 equivalents of fluoride ions relative to the substrate.

[0113] The reaction is preferably carried out in a solvent. Any solvent that is not harmful to the reaction can be used, including aromatic hydrocarbon solvents such as benzene, toluene, xylene, and chlorobenzene; aliphatic hydrocarbon solvents such as pentane, hexane, and octane; ether solvents such as diethyl ether, diisopropyl ether, cyclopentyl methyl ether, tetrahydrofuran, dimethoxyethane, and 1,4-dioxane; ketone solvents such as acetone, methyl ethyl ketone, and cyclohexanone; halogenated solvents such as chloroform and dichloromethane; nitrile solvents such as acetonitrile and propionitrile; ester solvents such as ethyl acetate, propyl acetate, butyl acetate, and methyl propionate; amide solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; alcohol solvents such as methanol, ethanol, 1-propanol, 2-propanol, and tert-butanol; dimethyl sulfoxide; water; and mixtures thereof.

[0114] The reaction can be carried out at a temperature appropriately selected from the range of 0°C to 200°C, although this temperature varies depending on the acid used and the reaction conditions. After completion of the reaction, the target product can be obtained by ordinary post-treatment procedures, but if necessary, it can also be purified by column chromatography, recrystallization, or the like. In this step, instead of the silyl ether derivative (22), 1S,2R-(4) and 1R,2S-(4) obtained by the asymmetric reaction in step-1 are used as starting materials, and steps-2, -3, -4, -5 and -6, or steps-2, -3, -4, -5 and -8 are carried out to obtain each isomer of the silyl ether derivative (22), while maintaining its stereochemistry.

[0115] [Manufacturing method 13]

[0116] [ka]

[0117] (R4 and R 5 has the same meaning as above.) Step 13 is a step of producing a 1,4-cineole derivative (25) by reducing the olefin derivative represented by formula (24). The resulting 1,4-cineole derivative (25) is a mixture of 3R-(25) and 3S-(25), and can be easily separated and purified by column chromatography or the like. The reduction method used in this reaction may include a method using a reducing agent such as zinc powder, reduced iron, tin powder, stannous chloride, or titanium chloride; a method using a hydrogen donor such as hydrazine in the presence of Raney nickel; catalytic hydrogen reduction in the presence of a catalyst such as Raney nickel, palladium on carbon, palladium hydroxide, platinum oxide, or rhodium on carbon; or catalytic hydrogen transfer reduction.

[0118] The reaction is preferably carried out in a solvent. Any solvent that is not harmful to the reaction can be used, including aromatic hydrocarbon solvents such as benzene, toluene, xylene, and chlorobenzene; aliphatic hydrocarbon solvents such as pentane, hexane, and octane; ether solvents such as diethyl ether, diisopropyl ether, cyclopentyl methyl ether, tetrahydrofuran, dimethoxyethane, and 1,4-dioxane; ketone solvents such as acetone, methyl ethyl ketone, and cyclohexanone; halogenated solvents such as chloroform and dichloromethane; nitrile solvents such as acetonitrile and propionitrile; ester solvents such as ethyl acetate, propyl acetate, butyl acetate, and methyl propionate; amide solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; alcohol solvents such as methanol, ethanol, 1-propanol, 2-propanol, and tert-butanol; dimethyl sulfoxide; water; and mixtures thereof.

[0119] The reaction can be carried out at a temperature appropriately selected from the range of 0°C to 200°C, although this temperature varies depending on the reaction conditions. After completion of the reaction, the target product can be obtained by ordinary post-treatment procedures, but if necessary, it can also be purified by column chromatography, recrystallization, or the like. In this step, instead of the olefin derivative (24), 1S,2R-(4) and 1R,2S-(4) obtained by the asymmetric reaction in step-1 are used as starting materials to carry out steps-2, 3, 4, 5, 6, and 12 to obtain the isomers of the olefin derivative (24), thereby obtaining each isomer while maintaining its stereochemistry.

[0120] [Manufacturing method 14]

[0121] [ka]

[0122] (R 1 , R 2a , R 3a , Y has the same meaning as above.) Step 14 is a step of producing a 1,4-cineole derivative (27) by reacting a compound represented by formula (26) with the 2-hydroxyl group of a 1,4-cineole derivative represented by formula (21). This reaction may be carried out in the presence of a base, and examples of the base include organic bases such as triethylamine, diisopropylethylamine, tributylamine, propylamine, butylamine, tert-butylamine, benzylamine, N-methylmorpholine, N,N-dimethylaniline, N,N-diethylaniline, 4-tert-butyl-N,N-dimethylaniline, pyridine, 4-dimethylaminopyridine, picoline, lutidine, pyrazine, imidazole, and N-methylimidazole, and alkali metal salts such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium acetate, potassium acetate, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydride, potassium hydride, sodium amide, butyllithium, tert-butyllithium, lithium diisopropylamide, trimethylsilyllithium, and lithium hexamethyldisilazide. The target product can be obtained in good yield by using 0.1 to 10 equivalents of the base relative to the substrate.

[0123] The solvent used in this reaction can be any solvent that is not harmful to the reaction, and examples thereof include aromatic hydrocarbon solvents such as benzene, toluene, xylene, and chlorobenzene; aliphatic hydrocarbon solvents such as pentane, hexane, and octane; ether solvents such as diethyl ether, diisopropyl ether, cyclopentyl methyl ether, tetrahydrofuran, dimethoxyethane, and 1,4-dioxane; ketone solvents such as acetone, methyl ethyl ketone, and cyclohexanone; halogenated solvents such as chloroform and dichloromethane; nitrile solvents such as acetonitrile and propionitrile; ester solvents such as ethyl acetate, propyl acetate, butyl acetate, and methyl propionate; amide solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; alcohol solvents such as methanol, ethanol, 1-propanol, 2-propanol, and tert-butanol; dimethyl sulfoxide; water; and mixtures thereof. The reaction can be carried out at a temperature appropriately selected from the range of 0°C to 200°C, although this temperature varies depending on the base used and the reaction conditions. After completion of the reaction, the target product can be obtained by ordinary post-treatment procedures, but if necessary, it can also be purified by column chromatography, recrystallization, or the like. In this step, instead of the 1,4-cineole derivative (21), 1S,2R-(4) and 1R,2S-(4) obtained by the asymmetric reaction in step-1 are used as starting materials to carry out the subsequent steps to obtain the respective isomers of the 1,4-cineole derivative (21), whereby each isomer can be obtained while retaining its stereochemistry.

[0124] [Manufacturing method 15]

[0125] [ka]

[0126] (R 1 , X a , Y has the same meaning as above.) Step 15 is a step of producing a 1,4-cineole derivative (28) by reacting a compound represented by formula (26) with the 2-hydroxyl group of a 1,4-cineole derivative represented by formula (23). This reaction may be carried out in the presence of a base, and examples of the base that can be used include organic bases such as triethylamine, diisopropylethylamine, tributylamine, propylamine, butylamine, tert-butylamine, benzylamine, N-methylmorpholine, N,N-dimethylaniline, N,N-diethylaniline, 4-tert-butyl-N,N-dimethylaniline, pyridine, 4-dimethylaminopyridine, picoline, lutidine, pyrazine, imidazole, and N-methylimidazole; and alkali metal salts such as sodium carbonate, potassium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate, sodium acetate, potassium acetate, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydride, potassium hydride, sodium amide, butyllithium, tert-butyllithium, sec-butyllithium, lithium diisopropylamide, trimethylsilyllithium, sodium hexamethyldisilazide, potassium hexamethyldisilazide, lithium diisopropylamide, trimethylsilyllithium, and lithium hexamethyldisilazide. The target product can be obtained in good yield by using 0.1 to 10 equivalents of the base relative to the substrate in the reaction.

[0127] The solvent used in this reaction can be any solvent that is not harmful to the reaction, and examples thereof include aromatic hydrocarbon solvents such as benzene, toluene, xylene, and chlorobenzene; aliphatic hydrocarbon solvents such as pentane, hexane, and octane; ether solvents such as diethyl ether, diisopropyl ether, cyclopentyl methyl ether, tetrahydrofuran, dimethoxyethane, and 1,4-dioxane; ketone solvents such as acetone, methyl ethyl ketone, and cyclohexanone; halogenated solvents such as chloroform and dichloromethane; nitrile solvents such as acetonitrile and propionitrile; ester solvents such as ethyl acetate, propyl acetate, butyl acetate, and methyl propionate; amide solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; alcohol solvents such as methanol, ethanol, 1-propanol, 2-propanol, and tert-butanol; dimethyl sulfoxide; water; and mixtures thereof.

[0128] The reaction can be carried out at a temperature appropriately selected from the range of 0°C to 200°C, although this temperature varies depending on the base used and the reaction conditions. After completion of the reaction, the target product can be obtained by ordinary post-treatment procedures, but if necessary, it can also be purified by column chromatography, recrystallization, or the like. In this step, instead of the 1,4-cineole derivative (23), 1S,2R-(4) and 1R,2S-(4) obtained by the asymmetric reaction in step-1 are used as starting materials to carry out the subsequent steps to obtain the respective isomers of the 1,4-cineole derivative (23), whereby each isomer can be obtained while retaining its stereochemistry.

[0129] The compound of the present invention and the intermediate of the present invention may be analyzed by melting point, infrared absorption spectrum, 1 H-NMR, 13 It can be analyzed, confirmed, and identified by C-NMR, mass spectrometry, X-ray structural analysis, etc. The compound of the present invention is not limited to the above-mentioned production method, and can be produced by any organic synthesis method.

[0130] The present invention also relates to a herbicide containing the compound of the present invention as an active ingredient (hereinafter also referred to as "the herbicide of the present invention"). The herbicide of the present invention is preferably for use on agricultural land, pasture, turf, or non-agricultural land. Examples of agricultural land include farmland, paddy fields, orchards, fallow land, and uncultivated land.

[0131] As will be shown in the test examples described later, the compounds of the present invention exhibit excellent herbicidal activity and also exhibit excellent selective herbicidal activity between the weeds and crops shown below, and therefore can be used against a wide range of weeds in paddy rice and upland crops. Specific examples of weeds include the following:

[0132] Specifically, for example, barnyardgrass (Echinochloa crus-galli), oryzicola, crabgrass (Digitaria sanguinalis, Digitaria ischaem, Digitaria adscendens, Digitaria microbachne, Digitaria horizontalis), green foxtail (Setaria Viridis), foxtail (Setaria faberi), golden foxtail (Setaria lutescens), goosegrass (Eleusine indica), oat (Avena fatua), Sorghum halepense, wheatgrass (Aropyron repens), velvet millet (Brachiaria plantaginea), oat millet (Panicum maximum), paragrass (Panicum purpurascens), and large foxtail (Panicum dichotomiflorum, Leptochloa chinensis, Leptochloa panicea, Poa annua, Alopecurus aequalis, Alopecurus myosuroides, Wheatgrass (Agropyron tsukushiense), American millet (Brachiaria platyphylla), Cenchrus echinatus, Lolium multiflorum, Cynodon dactylon, Beckmannia syzigache, Bromus catharticus, Leersia japonica, Leersia sayanuka, Lolium Gramineae weeds such as (Phleum rigidum), knotgrass (Paspalum distichum), and timothy grass (Phleum pratense);Cyperaceae weeds such as Cyperus iria, Cyperus rotundus, Cyperus esculentus, Scirpus hotarui, Cyperus serotinus, Cyperus serotinus, Eleocharis acicularis, Eleocharis kuroguwai, Cyperus flaccidus, Kyllinga brevifolia, and Scirpus juncoides; Sagittaria pygmaea, Sagittaria trifolia, and Alisma aegyptiaca Weeds of the family Alismataceae, such as Monochoria canaliculatum; weeds of the family Pontderiaceae, such as Monochoria vaginalis, Heteranthera limosa, and Monochoria kosakowii; weeds of the family Lindernia pyxidaria; weeds of the family Plantaginaceae, such as Plantago asiatica, Gratiola japonica, Dopatrium junceum, and Veronica polita; weeds of the family Lythraceae, such as Rotala india and Lythrum americanum; weeds of the family Elatine triandra; malvaceae, such as velvetleaf (Abutiol theophrsti) and sedge (Sida spinosa);Compositae weeds such as cocklebur (Xanthium strumarim), ragweed (Ambrosia elatior), snow thistle (Breea serosa), ash weed (Galinsoga ciliata), chamomile (Matricaria chamomilla), dandelion (Taraxacum officinale), artemisia (Erigeron canadensis), Bidens frondosa, Bidens pilosa, Bidens tripartita, chickweed (Gnaphalium affine), and groundsel (Senecio vulgaris); Lamiaceae weeds such as nightshade (Lamium amplexinale weber); nightshade (Solanum Solanaceae weeds such as Datura stramonium (Datura stramonium), Amaranthaceae weeds such as Amaranthus viridis (Amaranthus viridis), Chenopodium album (Chenopodium album), Kochia scoparia (Kochia scoparia), and Amaranthus hybridus (Amaranthus hybridus); Polygonaceae weeds such as Polygonum lapathifolium (Polygonum lapathifolium), Polygonum persicaria (Polygonum convolvulus), Polygonum aviculare (Polygonum aviculare), Persicaria longiseta (Persicaria nepalensis), Cardamine flexuosa (Cardamine flexuosa), and Shepherd's purse (Capsella bursapastoris), common mustard (Brassica juncea), and dog mustard (Rorippa indica);Convolvulaceae weeds such as Ipomoea purpurea, Convolvulus arvensis, Ipomoea hederacea, Calystegia pubescens, and Ipomoea coccinea; Portulacaceae weeds such as Portulaca aleracea; Legume weeds such as Cassia obtusifolia, Aeschynomene indica, Sesbania exaltata, Trifolium repens, and Vicia sativa; and Stellaria media, Stellaria neglecta, and Stellaria Caryophyllaceae (Caryophyllaceae) such as Euphorbia helioscopia and Acalypha australis; Commelinaceae (Commelinaceae) such as Commelina communis and Murdannia keisak; Potamogetonaceae (Potamogeton distinctus) and other pondweeds; Araceae (Araceae) such as Spirodela polyrhiza; Cucurbitaceae (Cucurbitaceae) such as Sicyos angulatus; Rubiaceae (Rubiaceae) such as Galium spurium; and Oenanthe Apiaceae weeds such as Viola javanica; Violaceae weeds such as Viola mandshuria; Onagraceae weeds such as Ludwigia epilobioides and Oenothera odorata;It can control a variety of noxious weeds, including weeds from the Oxalidaceae family (such as wood sorrel (Oxalis corniculata)); weeds from the Equisetaceae family (such as horsetail (Equisetum arvense)); and weeds from the Zygnemataceae family (such as Spirogyra sp.). Therefore, it can be effectively used to selectively or non-selectively control noxious weeds in the cultivation of useful crops such as corn (Zea mays), soybean (Glycine max), cotton (Gossypium spp.), wheat (Triticum spp.), barley (Hordeum vulgare), rye (Secalecereale), oats (Avena sativa), sorghum (Sorghum bicolor), rapeseed (Brassica napus), sunflower (Helianthus annuus), sugar beet (Beta vulgaris), sugarcane (Saccharum officinarum), grass (Zoysia japonicaa), peanut (Arachis hypogaea), flax (Linum usitatissmum), tobacco (Nicotiana tabacum), and coffee (Coffea spp.); It should be noted that the application of the herbicide of the present invention is not limited to the weeds and crops exemplified above.

[0133] The compound of the present invention may be mixed with other herbicides, various insecticides, acaricides, nematicides, fungicides (fungicides, bactericides, antivirals, plant resistance inducers), bird repellents, plant growth regulators, phytotoxicity safeners, fertilizers, soil improvers, synergists, etc. at the time of formulation or spraying, as required, or may be mixed and applied in a tank mix at the time of spraying. In particular, by applying it in combination with other herbicides, the amount of herbicide used can be reduced, saving labor, and the synergistic action of both herbicides can expand the range of herbicides that can be applied (herbicide spectrum), and it is expected that an even stronger effect can be obtained through the synergistic action of both herbicides.In this case, it is also possible to combine and formulate multiple known herbicides and phytotoxicity safeners at the same time.

[0134] Among the optional ingredients, representative examples of herbicides are shown below, but are not limited to these. (1) 2,4-D, 2,4-D-butotyl, 2,4-D-butyl, 2,4-D-dimethylammonium, 2,4-D-diolamine, 2,4-D-ethyl, 2,4-D-2-ethylhexyl, 2,4-D-isobutyl, 2,4-D-isoctyl, 2,4-D-isopropyl, 2,4-D-isopropylammonium 2,4-DB, 2,4-DB-butyl, 2,4-DB-dimethylammonium, 2,4-DB-isooctyl, 2,4-DB-potassium, 2,4-DB-sodium, 2,4-D choline salt (2,4-D) chloinesalt, dichlorprop, dichlorprop-butotyl, dichlorprop-dimethylammonium, dichlorprop-isoctyl, dichlorprop-potassium, dichlorprop-P, dichlorprop-P-dimethylammonium, dichlorprop-P-potassium, dichlorprop-P-sodium, MCPA, MCPA-butotyl, MCPA-dimethylammonium,MCPA-2-ethylhexyl, MCPA-potassium, MCPA-sodium, MCPA-thioethyl, MCPB, MCPB-ethyl, MCPB-sodium, mecoprop, mecoprop-butotyl, mecoprop-sodium, mecoprop-P Phenoxy compounds such as mecoprop-P, mecoprop-P-butotyl, mecoprop-P-dimethylammonium, mecoprop-P-2-ethylhexyl, mecoprop-P-potassium, naproanilide, clomeprop, and HIA-1; 2,3,6-TBA, and dicamba a), dicamba-butotyl, dicamba-diglycolamine, dicamba-dimethylammonium, dicamba-diolamine, dicamba-isopropylammonium, dicamba-potassium, dicamba-sodium, picloram, picloram-dimethylammonium, picloram-isoctyl, picloram-potassium, picloram-triisopropanolammonium, picloram-triisopropylammonium, picloram-trolamine,Aromatic carboxylic acid compounds such as triclopyr, triclopyr-butotyl, triclopyr-triethylammonium, clopyralid, clopyralid-olaammine, clopyralid-potassium, clopyralid-triisopropanolammonium, aminopyralid, aminocyclopyrachlor, aminocyclopyrachlor, halauxifen, florpyrauxifen, halauxifen-methyl, and DAS-534; and others, naphtha Compounds that are said to exhibit herbicidal activity by disrupting plant hormone action, such as naptalam, naptalam sodium, benazolin, benazolin ethyl, quinclorac, quinmerac, diflufenzopyr, diflufenzopyr sodium, fluroxypyr, fluroxypyr-2-butoxy-1-methylethyl, fluroxypyr-meptyl, chlorflurenol, chlorflurenol-methyl, clacyfos, and fluchloraminopyr.

[0135] (2) chlorotoluron, diuron, fluometuron, linuron, isoproturon, metobenzuron, tebuthiuron, dimefuron, isouron, karbutilate, methabenzthiazolone Urea compounds such as zuron, metoxuron, metoburomuron, monolinuron, neburon, siduron, terbumeton, and trietazine; simazine, atrazine, atratone, simetryn, and prometryn Triazine compounds such as prometryn, dimethametryn, hexazinone, metribuzin, terbuthylazine, cyanazine, ametryn, cybutryne, terbutryn, propazine, metamitron, and prometon; uracil compounds such as bromacil, bromacil lithium, lenacil, and terbacil; anilide compounds such as propanil and cypromid; carbamate compounds such as swep, desmedipham, and phenmedipham;Hydroxybenzonitrile compounds such as bromoxynil, bromoxynil octanoate, bromoxynil heptanoate, ioxynil, ioxynil octanoate, ioxynil potassium, and ioxynil sodium; and other compounds that are believed to exhibit herbicidal activity by inhibiting plant photosynthesis, such as pyridate, bentazone, bentazone sodium, amicarbazone, methazole, pentanochlor, and phenmedipham.

[0136] (3) Quaternary ammonium salt compounds such as paraquat and diquat, which are believed to become free radicals in plants, generating active oxygen and exhibiting rapid-acting herbicidal effects.

[0137] (4) Nitrofen, chlomethoxyfen, bifenox, acifluorfen, acifluorfen sodium, fomesafen, fomesafen sodium, oxyfluorfen, lactofen, aclonifen, ethoxyfen-ethyl diphenyl ether compounds such as fluoroglycofen-ethyl, fluoroglycofen; cyclic imide compounds such as chlorphthalim, flumioxazin, flumiclorac, flumiclorac-pentyl, cinidon-ethyl, fluthiacet-methyl, EK-5385;Others include oxadiargyl, oxadiazon, sulfentrazone, carfentrazone-ethyl, thidiazimine, pentoxazone, azafendizone, isopropazole, pyraflufen-ethyl, benzfendizone, butafenacil, saflufenacil, fluazolate, and profluazole. Compounds that are believed to exhibit herbicidal activity by inhibiting plant chlorophyll biosynthesis and causing abnormal accumulation of photosensitized peroxides in the plant body, such as uazol, flufenpyr-ethyl, bencarbazone, thiafenacil, pyrachlonil, cyclopyranil, epirifenacil, trifludimoxazin, flufenoximacil, HNPC-B4047, IR-6396, EK-5498, SYN-523, and compounds described in WO2008 / 008763 (FMC);

[0138] (5) pyridazinone compounds such as norflurazon, chloridazon, and metolflurazon; pyrazole compounds such as pyrazolinate, pyrazoxyfen, benzofenap, topramezone, pyrasulfotole, tolpyralate, tripyrasulfone, fenpyrazone, and bipyrazone;Others include amitrole, fluridone, flurtamone, diflufenican, methoxyphenone, clomazone, biclozone, sulcotrione, mesotrione, tembotrione, tefuryltrione, fenquinotrione, lancotrione, dioxopyritrione, benquitrione, cyclopyrimorate, and isoxaflutole. Compounds that are believed to inhibit the biosynthesis of plant pigments such as carotenoids and exhibit herbicidal activity characterized by bleaching, such as soxaflutole, difenzoquat, difenzoquat-methylsulfate, isoxachlorotol, benzobicyclon, bicyclopyron, picolinafen, beflubutamid, beflubutamid-M, ketospiradox, ketospiradox-potassium, and compounds described in JP2012 / 2571 (Sumitomo Chemical);

[0139] (6) Diclofop-methyl, diclofop, pyrifenonap-sodium, fluazifop-butyl, fluazifop, fluazifop-P, fluazifop-P-butyl, haloxyfop, haloxyfop-ethotyl, haloxyfop- P (haloxyfop-P), haloxyfop-P-methyl, quizalofop-ethyl, quizalofop-P (quizalofop-P), quizalofop-P-ethyl, quizalofop-P-tefuryl, cyhalofop-butyl, fenoxaprop-ethyl, fenoxaprop-P (f Aryloxyphenoxypropionic acid compounds such as enoxaprop-P, fenoxaprop-P-ethyl, metamifop-propyl, metamifop, clodinafop-propargyl, propaquizafop, HNPC-A8169, and SYP-1924; alloxydim-sodium, alloxydim Compounds that inhibit the biosynthesis of fatty acids and are said to have herbicidal effects on plants, such as cyclohexanedione compounds such as loxydim, crethodim, sethoxydim, tralkoxydim, butroxydim, tepraloxydim, profoxydim, and cycloxydim; phenylpyrazoline compounds such as pinoxaden; and the like.

[0140] (7) Chlorimuron-ethyl, chlorimuron, sulfometuron-methyl, sulfometuron, primisulfuron-methyl, primisulfuron, bensulfuron-methyl, bensulfuron, chlorsulfuron, methos metsulfuron-methyl, metsulfuron, cinosulfuron, pyrazosulfuron-ethyl, pyrazosulfuron, flazasulfuron, rimsulfuron, nicosulfuron, imazosulfuron, flucetosulfuron furon, cyclosulfamuron, prosulfuron, flupyrsulfuron-methyl-sodium, flupyrsulfuron, triflusulfuron, flupyrsulfuron-methyl-sodium, flupyrsulfuron, triflusulfuron, flupyrsulfuron-methyl-sodium, flupyrsulfuron, triflusulfuron methyl triflusulfuron-methyl, triflusulfuron, halosulfuron-methyl, halosulfuron, thifensulfuron-methyl, thifensulfuron, ethoxysulfuron, oxasulfuron, ethametsulfuron,Ethametsulfuron-methyl, iodosulfuron, iodosulfuron-methyl-sodium, sulfosulfuron, triasulfuron, tribenuron-methyl, tribenuron, tritosulfuron, foramsulfuron furon, trifloxysulfuron, trifloxysulfuron sodium, mesosulfuron-methyl, mesosulfuron, orthosulfamuron, amidosulfuron, azimsulfuron, propyrisulfuron, metazosulfuron sulfonylurea compounds such as metazosulfuron, methiopyrsulfuron, monosulfuron-methyl, orthosulfuron, iofensulfuron, and iofensulfuron-sodium; flumetsulam, metosulam, diclosulam, and cloransulfuron; Triazolopyrimidine sulfonamide compounds such as cloransulam-methyl, florasulam, penoxsulam, and pyroxsulam; imazapyr, imazapyr-isopropylammonium, imazethapyr, imazethapyr-ammonium, and imazaquin;Imidazolinone compounds such as imazaquin-ammonium, imazamox, imazamox-ammonium, imazamethabenz, imazamethabenz-methyl, and imazapic; pyrithiobac-sodium, bispyribac-sodium, and pyriminobac Pyrimidinylsalicylic acid compounds such as pyriminobac-methyl, pyribenzoxim, pyriftalid, pyrimisulfan, and triafamone; sulfonylaminocarbonyltriazolinone compounds such as flucarbazone, flucarbazone-sodium, propoxycarbazone-sodium, propoxycarbazone, and thiencarbazone-methyl; and others, such as glyphosate, glyphosate-sodium, glyphosate-potassium, glyphosate-ammonium, glyphosate-isopropylammonium, and glyphosate-isopropylammonium. Glyphosate-trimesium, glyphosate-sesquisodium, glufosinate, glufosinate-ammonium, glufosinate-P, glufosinate-P-ammonium, glufosinate-P-sodium, bilanafos,Compounds such as bilanafos sodium and cinmethylin are believed to exert their herbicidal effects by inhibiting amino acid biosynthesis in plants.

[0141] (8) Dinitroaniline compounds such as trifluralin, oryzalin, nitralin, pendimethalin, ethalfluralin, benfluralin, prodiamine, butralin, and dinitramine; amide compounds such as bensulide, napropamide, napropamide-M, propyzamide, and pronamide; organophosphorus compounds such as amiprofos-methyl, butamifos, anilofos, and piperophos; propham and chlorpropham Phenylcarbamate compounds such as opham, barban, and carbetamide; cumylamine compounds such as daimuron, cumyluron, bromobutide, and methyldymron; and other compounds that are believed to exert their herbicidal effect by inhibiting plant cell mitosis, such as asulam, asulam sodium, dithiopyr, thiazopyr, chlorthal-dimethyl, chlorthal, diphenamid, flamprop-M-methyl, flamprop-M, and flamprop-M-isopropyl.

[0142] (9) alachlor, metazachlor, butachlor, pretilachlor, metolachlor, S-metolachlor, thenylchlor, pethoxamid, acetochlor, propachlor, dimethenamide, dimethenamide - Chloroacetamide compounds such as dimethenamide-P, propisochlor, and dimethachlor; molinate, dimepiperate, pyributicarb, EPTC, butyrate, vernolate, cycloate, prosulfocarb, and esprocarb ), thiobencarb, diallate, tri-allate, orbencarb, and other thiocarbamate compounds; etobenzanid, mefenacet, flufenacet, tridiphane, cafenstrole, fentrazamide, ipfencarbazone, etc. Compounds that are said to exhibit herbicidal activity by inhibiting plant protein or lipid biosynthesis, such as pfncarbazone, oxaziclamefone, indanofan, benfuresate, pyroxasulfone, fenoxasulfone, methiozolin, dalapon, dalapon-sodium, TCA-sodium, and trichloroacetic acid.

[0143] (10) Compounds that are said to exhibit herbicidal activity by inhibiting cellulose biosynthesis in plants, such as dichlobenil, triaziflam, indaziflam, flupoxam, and isoxaben.

[0144] (11) tetflupyrolimet, dimesulfazet, rimisoxafen, MSMA, DSMA, CMA, endothall, endothall dipotassium, endothall sodium, endothall mono(N,N-dimethylalkylammonium), ethofumesate, sodium chlorate, pelargonic acid, nonanoic acid, fosamine, fosamine ammonium, acrolein, ammonium sulfamate, borax, chloroacetic acid, sodium chloroacetate chloroacetate, cyanamide, methylarsonic acid, dimethylarsonic acid, sodium dimethylarsonate, dinoterb, dinoterb-ammonium, dinoterb-diolamine, dinoterb-acetate, DNOC, ferrous sulfate, flupropanate, flupropanate-sodium, mefluidide, mefluidide-diolamine, metam, metam-ammonium, metam-potassium, metam-sodium, methyl isothiocyanateisothiocyanate, pentachlorophenol, sodium pentachlorophenoxide, pentachlorophenol laurate, quinoclamine, sulfuric acid, urea sulfate, zanthinosin, herbimycin, unguinol, metatyrosine, sarmentine, thaxtomin A, mevalocidin, alpha-limonene, pyribambenzpropyl, pyribambenzisopropyl z-isopropyl), pyriflubenzoxime, cypyrafluone JS-913, KHG-23844, H-9201, SIOC-0163, SIOC-0171, SIOC-0172, SIOC-0285, SIOC-0426, SIOC-H-057, ZJ-0166, ZJ-1835, ZJ-0453, ZJ-0777, ZJ-0862, and other herbicides such as compounds described in WO2008 / 096398 (Kumiai Chemical).

[0145] (12) Weeds that are said to exhibit herbicidal effects by parasitizing plants, such as Xanthomonas campestris, Epicoccosirus nematosorus, Epicoccosirus nematosperus, Exserohilum monoseras, and Drechsrela monoceras.

[0146] When the compound of the present invention is used as a herbicide, it can be used as it is, or it can be formulated and used. In the formulation, suitable carriers, adjuvants, surfactants, binders, stabilizers, etc. described in Pesticide Formulation Guide (edited by the Pesticide Science Society of Japan Application Method Research Group, published by the Japan Plant Protection Association, 1997) may be blended.

[0147] The herbicide containing the compound of the present invention can be formulated into any commonly used dosage form, and can be used in the form of, for example, granules, microgranules, fine granules, wettable powders, wettable granules (dry flowable) formulations, emulsifiable concentrates, water-soluble formulations, sols (flowable formulations), liquid formulations, dusts, coarse dusts, DL (driftless type) dusts, flow dust formulations, oil formulations, microcapsules, pastes, jumbo formulations, etc., but is not limited to these.

[0148] The carrier used in formulation can be either solid or liquid, as long as it is a carrier commonly used in pesticide formulations. Such carriers are not limited to specific ones, but specific examples include the following. Solid carriers include, for example, mineral powders (kaolin, bentonite, clay, montmorillonite, talc, diatomaceous earth, mica, vermiculite, quartz, calcium carbonate, apatite, white carbon, slaked lime, silica sand, acid clay, zeolite, sepiolite, expanded perlite pulverized products, shirasu balloons, alumina balloons, microspheres made of phenolic resins, epoxy resins, polyacrylonitrile, polyurethane, etc.), vegetable powders (soybean flour, wheat flour, wood flour, tobacco powder, starch, crystalline cellulose, etc.), polymeric compounds (petroleum resins, polyvinyl chloride, ketone resins, etc.), alumina, silicates, glucose, sucrose, lactose, sugar polymers, ammonium sulfate, sodium chloride, potassium chloride, urea, highly dispersible silicic acid, waxes, etc. Examples of liquid carriers include water, alcohols (methyl alcohol, ethyl alcohol, n-propyl alcohol, isopropyl alcohol, butanol, ethylene glycol, benzyl alcohol, etc.), aromatic hydrocarbons (toluene, benzene, xylene, ethylbenzene, methylnaphthalene, etc.), ethers (ethyl ether, ethylene oxide, dioxane, tetrahydrofuran, etc.), ketone solvents (acetone, methyl ethyl ketone, cyclohexanone, methyl isobutyl ketone, isophorone, etc.), esters (ethyl acetate, butyl acetate, ethylene glycol acetate, amyl acetate, etc.), acid amides (dimethylformamide, dimethylacetamide, etc.), nitriles (acetonitrile, propionitrile, acrylonitrile, etc.), sulfoxides (dimethyl sulfoxide, etc.), alcohol ethers (ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, etc.), aliphatic or alicyclic hydrocarbons (n-hexane, cyclohexane, etc.), industrial gasoline (petroleum ether, solvent naphtha, etc.), petroleum fractions (paraffins, kerosene, diesel, etc.), and the like.

[0149] When herbicides are formulated into emulsifiable concentrates, wettable powders, flowables, etc., various surfactants are added for the purposes of emulsification, dispersion, solubilization, wetting, foaming, lubrication, spreading, etc. Examples of such surfactants include nonionic surfactants such as polyoxyethylene alkyl ethers, polyoxyethylene alkyl esters, polyoxyethylene sorbitan alkyl esters, polyoxyethylene alkylaryl ethers, polyoxyethylene polyoxypropylene block polymers, and polyoxyethylene styryl phenyl ethers; anionic surfactants such as alkylbenzenesulfonates, alkyl sulfosuccinates, alkyl sulfates, polyoxyethylene alkyl sulfates, arylsulfonates, alkylnaphthalenesulfonates, polyoxyethylene styryl phenyl ether sulfates, ligninsulfonates, naphthalenesulfonic acid formaldehyde condensates, and polycarboxylates; cationic surfactants such as alkylamines (laurylamine, stearyltrimethylammonium chloride, etc.), polyoxyethylene alkylamines, alkylpyridinium salts, alkyltrimethylammonium salts, and alkyldimethylammonium salts; and amphoteric surfactants such as carboxylic acids (betaine type) and sulfate ester salts. However, the present invention is not limited to these examples. In addition to these, various adjuvants and additives such as polyvinyl alcohol (PVA), carboxymethyl cellulose (CMC), gum arabic, polyvinyl acetate, sodium alginate, gelatin, tragacanth gum, dextrin, hydroxypropyl methyl cellulose (HPMC), and methyl cellulose (MC) can also be used.

[0150] Preferred methods of application of the herbicide containing the compound of the present invention as an active ingredient include soil application, water surface application, and foliage application, and particularly excellent effects can be obtained by application from before germination of the weeds to when they are young shoots. The amount of the compound of the present invention to be applied as a herbicide varies depending on the application site, application time, application method, target weeds, cultivated crops, etc., but generally, the appropriate amount of active ingredient is about 0.001 to 10 kg per hectare (ha), preferably about 0.01 to 1 kg.

[0151] The present invention also relates to a method for using the herbicide of the present invention, which comprises applying an effective amount of the compound of the present invention to at least one selected from the foliage of weeds, soil, and water surface. The weeds are not particularly limited, but include, for example, the weeds mentioned above. The soil is preferably farmland such as upland or paddy fields where agricultural and horticultural plants are cultivated. The water surface may be the water surface in waterlogged soil. The treatment step is not particularly limited, and examples thereof include a step of spraying an effective amount of the compound of the present invention onto at least one selected from the foliage of weeds, soil, and water surfaces.

[0152] Furthermore, the present invention relates to a method for preparing an agricultural chemical composition, which comprises a step of mixing a herbicide containing the compound of the present invention as an active ingredient with at least one selected from an extender and a surfactant. The extender is not particularly limited, but examples thereof include natural minerals such as clay, quartz, calcite, sepiolite, dolomite, chalk, kaolin, pyrophyllite, sericite, halloysite, metahaloysite, kibushi clay, gairome clay, pottery stone, ziglite, allophane, shirasu, kira, talc, pumice, hectorite, zeolite, and diatomaceous earth; calcined products of natural minerals such as calcined clay, perlite, shirasu balloon, vermiculite, attapulgus clay, and calcined diatomaceous earth; magnesium carbonate, calcium carbonate; Examples of suitable inorganic salts include sodium carbonate, sodium hydrogen carbonate, ammonium sulfate, sodium sulfate, magnesium sulfate, diammonium hydrogen phosphate, ammonium dihydrogen phosphate, and potassium chloride; sugars such as glucose, fructose, sucrose, and lactose; polysaccharides such as starch, powdered cellulose, and dextrin; organic substances such as urea, urea derivatives, benzoic acid, and salts of benzoic acid; plants such as wood flour, corn cobs, walnut shells, and tobacco stalks; fly ash, white carbon, and water. The surfactant is not particularly limited, but examples thereof include the same surfactants as those described above in the formulation of herbicides. The method for mixing the herbicide containing the compound of the present invention as an active ingredient with at least one selected from an extender and a surfactant is not particularly limited, and known methods can be used. [Example]

[0153] The present invention will be explained in more detail below with reference to synthesis examples, formulation examples and test examples of the compounds of the present invention and intermediates of the present invention, but the present invention is not limited to these examples at all.

[0154] Synthesis Example 1 Synthesis of (1S,2R,3R,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-ol(1-24) p-Toluenesulfonic acid monohydrate (308 mg, 1.78 mmol) was added to a solution of (1R,2R,3S,6R)-6-isopropyl-3-methyl-2-[(2-methylbenzyl)oxy]-7-oxabicyclo[4.1.0]heptan-3-ol (518 mg, 1.78 mmol) in tetrahydrofuran (18 mL) and stirred at room temperature for 7 hours. Saturated aqueous sodium bicarbonate was poured into the reaction mixture, which was then extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane) to give the title compound (469 mg, 91%) as a colorless liquid.

[0155] Synthesis Example 2 Synthesis of (1S,2R,3R,4S)-3-(benzyloxy)-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-ol(1-22) p-Toluenesulfonic acid monohydrate (611 mg, 3.19 mmol) was added to a solution of (1R,2R,3S,6R)-2-(benzyloxy)-6-isopropyl-3-methyl-7-oxabicyclo[4.1.0]heptan-3-ol (828 mg, 3.00 mmol) in tetrahydrofuran (30 mL) and stirred at room temperature for 7 hours. Saturated aqueous sodium bicarbonate was poured into the reaction mixture, which was then extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane) to give the title compound (549 mg, 66%) as a colorless liquid.

[0156] Synthesis Example 3 Synthesis of (1S,2R,3R,4S)-3-[(2-chlorobenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-ol(1-32) To a solution (4 mL) of (1S,2R,3R,4S)-2-[(2-chlorobenzyl)oxy]-3-(1-ethoxyethoxy)-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]heptane (449 mg, 1.17 mmol) in tetrahydrofuran, 3N hydrochloric acid (1.56 mL) was added and stirred at room temperature for 3 hours. Saturated aqueous sodium bicarbonate was poured into the reaction mixture, which was then extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane) to give the title compound (348 mg, 96%) as a colorless liquid.

[0157] Synthesis Example 4 Synthesis of (1S,2R,3R,4S)-3-[(2,6-dimethylbenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-ol(1-26) In Synthesis Example 3, (1S,2R,3R,4S)-2-[(2,6-dimethylbenzyl)oxy]-3-(1-ethoxyethoxy)-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]heptane was used instead of (1S,2R,3R,4S)-2-[(2-chlorobenzyl)oxy]-3-(1-ethoxyethoxy)-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]heptane, and the same reaction and treatment were carried out, to obtain the title compound (yield 90%) as a colorless liquid.

[0158] Synthesis Example 5 Synthesis of (1S,2R,3R,4S)-1-isopropyl-3-[(2-methoxybenzyl)oxy]-4-methyl-7-oxabicyclo[2.2.1]heptan-2-ol(1-28) In Synthesis Example 3, (1S,2R,3R,4S)-2-[(2-chlorobenzyl)oxy]-3-(1-ethoxyethoxy)-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]heptane was replaced with (1S,2R,3R,4S)-2-(1-ethoxyethoxy)-1-isopropyl-3-[(2-methoxybenzyl)oxy]-4-methyl-7-oxabicyclo[2.2.1]heptane, and the same reaction and treatment were carried out to obtain the title compound (yield 95%) as a colorless liquid.

[0159] Synthesis Example 6 Synthesis of (1S,2R,3R,4S)-3-[(2-fluorobenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-ol(1-30) In Synthesis Example 3, (1S,2R,3R,4S)-2-(1-ethoxyethoxy)-3-[(2-fluorobenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptane was used instead of (1S,2R,3R,4S)-2-[(2-chlorobenzyl)oxy]-3-(1-ethoxyethoxy)-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]heptane, and the same reaction and treatment were carried out to obtain the title compound (yield 94%) as a colorless liquid.

[0160] Synthesis Example 7 Synthesis of (1S,2R,3R,4S)-3-[(2,3-difluorobenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-ol(1-35) In Synthesis Example 3, (1S,2R,3R,4S)-2-[(2,3-difluorobenzyl)oxy]-3-(1-ethoxyethoxy)-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]heptane was used instead of (1S,2R,3R,4S)-2-[(2,3-difluorobenzyl)oxy]-3-(1-ethoxyethoxy)-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]heptane, and the same reaction and treatment were carried out to obtain the title compound (yield 94%) as a white solid.

[0161] Synthesis Example 8 Synthesis of (1S,2R,3R,4S)-3-[(2,4-difluorobenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-ol(1-37) In Synthesis Example 3, (1S,2R,3R,4S)-2-[(2-chlorobenzyl)oxy]-3-(1-ethoxyethoxy)-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]heptane was used instead of (1S,2R,3R,4S)-2-[(2,4-difluorobenzyl)oxy]-3-(1-ethoxyethoxy)-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]heptane, and the same reaction and treatment were carried out to obtain the title compound (yield 92%) as a white solid.

[0162] Synthesis Example 9 Synthesis of (1S,2R,3R,4S)-3-[(2,5-difluorobenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-ol(1-39) In Synthesis Example 3, (1S,2R,3R,4S)-2-[(2,5-difluorobenzyl)oxy]-3-(1-ethoxyethoxy)-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]heptane was used instead of (1S,2R,3R,4S)-2-[(2,5-difluorobenzyl)oxy]-3-(1-ethoxyethoxy)-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]heptane, and the same reaction and treatment were carried out to obtain the title compound (yield 92%) as a white solid.

[0163] Synthesis Example 10 Synthesis of (1S,2R,3R,4S)-3-[(2,6-difluorobenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-ol(1-41) In Synthesis Example 3, (1S,2R,3R,4S)-2-[(2,6-difluorobenzyl)oxy]-3-(1-ethoxyethoxy)-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]heptane was used instead of (1S,2R,3R,4S)-2-[(2,6-difluorobenzyl)oxy]-3-(1-ethoxyethoxy)-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]heptane, and the same reaction and treatment were carried out to obtain the title compound (yield 95%) as a colorless liquid.

[0164] Synthesis Example 11 Synthesis of (1S,2R,3R,4S)-3-[(3,5-difluorobenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-ol(1-43) In Synthesis Example 3, (1S,2R,3R,4S)-2-[(3,5-difluorobenzyl)oxy]-3-(1-ethoxyethoxy)-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]heptane was used instead of (1S,2R,3R,4S)-2-[(3,5-difluorobenzyl)oxy]-3-(1-ethoxyethoxy)-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]heptane, and the same reaction and treatment were carried out to obtain the title compound (yield 92%) as a white solid.

[0165] Synthesis Example 12 Synthesis of (1S,2R,3R,4S)-1-isopropyl-4-methyl-3-[(perfluorophenyl)methoxy]-7-oxabicyclo[2.2.1]heptan-2-ol(1-45) In Synthesis Example 3, (1S,2R,3R,4S)-2-[(2-chlorobenzyl)oxy]-3-(1-ethoxyethoxy)-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]heptane was replaced with (1S,2R,3R,4S)-2-(1-ethoxyethoxy)-1-isopropyl-4-methyl-3-[(perfluorophenyl)methoxy]-7-oxabicyclo[2.2.1]heptane, and the same reaction and treatment were carried out to obtain the title compound (yield 45%) as a colorless liquid.

[0166] Synthesis Example 13 Synthesis of (1S,2R,3R,4S)-3-[(2,6-dichlorobenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-ol(1-47) In Synthesis Example 3, (1S,2R,3R,4S)-2-[(2,6-dichlorobenzyl)oxy]-3-(1-ethoxyethoxy)-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]heptane was used instead of (1S,2R,3R,4S)-2-[(2-chlorobenzyl)oxy]-3-(1-ethoxyethoxy)-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]heptane, and the same reaction and treatment were carried out, to obtain the title compound (yield 90%) as a colorless liquid.

[0167] Synthesis Example 14 Synthesis of (1S,2R,3R,4S)-1-isopropyl-4-methyl-3-[[2-(trifluoromethyl)benzyl]oxy]-7-oxabicyclo[2.2.1]heptan-2-ol(1-50) In Synthesis Example 3, (1S,2R,3R,4S)-2-(1-ethoxyethoxy)-1-isopropyl-4-methyl-3-[[2-(trifluoromethyl)benzyl]oxy]-7-oxabicyclo[2.2.1]heptane was used instead of (1S,2R,3R,4S)-2-[(2-chlorobenzyl)oxy]-3-(1-ethoxyethoxy)-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]heptane, and the same reaction and treatment were carried out to obtain the title compound (yield 88%) as a colorless liquid.

[0168] Synthesis Example 15 Synthesis of (1S,2R,3R,4S)-1-isopropyl-2-methoxy-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptane(1-141) Sodium hydride (23.2 mg, 0.533 mmol) was added to a solution of (1S,2R,3R,4S)-4-isopropyl-3-methoxy-1-methyl-7-oxabicyclo[2.2.1]heptan-2-ol (71.1 mg, 0.355 mmol) in dimethylformamide (3.6 mL) and stirred at room temperature for 1 hour. 2-Methylbenzyl bromide (0.048 mL, 0.355 mmol) was added to the reaction mixture and stirred for 22 hours and 30 minutes. Saturated aqueous ammonium chloride solution was poured into the reaction mixture, which was then extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane) to give the title compound as a colorless liquid (yield 76.7 mg, 71%).

[0169] Synthesis Example 16 Synthesis of (1S,2R,3R,4S)-1-isopropyl-2-methoxy-3-[(2-methoxybenzyl)oxy]-4-methyl-7-oxabicyclo[2.2.1]heptane(1-144) The same reaction and treatment were carried out as in Synthesis Example 15, except that 2-Methoxybenzyl bromide was used instead of 2-Methylbenzyl bromide, to give the title compound (yield 41%) as a colorless liquid.

[0170] Synthesis Example 17 Synthesis of (1S,2R,3R,4S)-2-[(2-fluorobenzyl)oxy]-4-isopropyl-3-methoxy-1-methyl-7-oxabicyclo[2.2.1]heptane(1-146) The same reaction and treatment were carried out as in Synthesis Example 15, except that 2-fluoroobenzyl bromide was used instead of 2-methylbenzyl bromide, to give the title compound (yield 25%) as a colorless liquid.

[0171] Synthesis Example 18 Synthesis of (1S,2R,3R,4S)-2-[(2-chlorobenzyl)oxy]-4-isopropyl-3-methoxy-1-methyl-7-oxabicyclo[2.2.1]heptane(1-148) The same reaction and treatment were carried out as in Synthesis Example 15, except that 2-chlorobenzyl bromide was used instead of 2-methylbenzyl bromide, to give the title compound (yield 21%) as a colorless liquid.

[0172] Synthesis Example 19 Synthesis of (1R,2R,3S,4R)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-ol(1-25) p-Toluenesulfonic acid monohydrate (118 mg, 0.647 mmol) was added to a solution (10 mL) of (1R,2S,3R,6R)-6-isopropyl-3-methyl-2-[(2-methylbenzyl)oxy]-7-oxabicyclo[4.1.0]heptan-3-ol (125 mg, 0.431 mmol) in tetrahydrofuran, and the mixture was stirred at room temperature for 8 hours. A saturated aqueous solution of sodium bicarbonate was poured into the reaction mixture, which was then extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane) to give the title compound (56.3 mg, 45%) as a colorless liquid.

[0173] Synthesis Example 20 Synthesis of O-[(1R,2R,3S,4R)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-yl) S-methyl carbonodithioate (1-217) Sodium hydride (36.1 mg, 0.506 mmol) was added to a solution of (1R,2R,3S,4R)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-ol (73.4 mg, 0.253 mmol) in tetrahydrofuran (3.0 mL) and stirred at 0 °C for 30 min. Carbon disulfide (0.031 mL, 0.51 mmol) and methyl iodide (0.032 mL, 0.51 mmol) were added to the reaction mixture and stirred for 2 h. The reaction mixture was concentrated under reduced pressure, poured into water, and extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane) to give the title compound as a colorless liquid (yield 90.8 mg, 94%).

[0174] Synthesis Example 21 Synthesis of (1S,2R,3R,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-yl trifluoromethanesulfonate (1-239) Pyridine (0.28 mL, 3.50 mmol) and trifluoromethanesulfonic anhydride (0.33 mL, 2.33 mmol) were added to a dichloromethane solution (12 mL) of (1S,2R,3R,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-ol (338 mg, 1.17 mmol) and stirred for 1 hour and 30 minutes. Saturated aqueous sodium bicarbonate solution was poured into the reaction mixture, which was then extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane) to give the title compound (399 mg, 93%) as a colorless liquid.

[0175] Synthesis Example 22 Synthesis of (1S,2R,3R,4S)-2-[(2-chlorobenzyl)oxy]-3-(1-ethoxyethoxy)-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]heptane(1-177) Sodium hydride (79.4 mg, 55% dispersion in mineral oil, 1.82 mmol) was added to a solution of (1S,2R,3R,4S)-3-(1-ethoxyethoxy)-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]heptan-2-ol (393 mg, 1.52 mmol) in dimethylformamide (15 mL) and stirred at 0°C for 1 hour. 2-Chlorobenzyl bromide (0.20 mL, 1.5 mmol) was added to the reaction mixture and stirred at room temperature for 2 hours. Water was poured into the reaction mixture, which was then extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane) to give the title compound (504 mg, 87%) as a colorless liquid.

[0176] Synthesis Example 23 Synthesis of (1S,2R,3R,4S)-2-[(2,6-dimethylbenzyl)oxy)-3-(1-ethoxyethoxy)-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]heptane(1-171) The same reaction and treatment were carried out as in Synthesis Example 22, except that 2,6-dimethylbenzyl bromide was used in place of 2-chlorobenzyl bromide, to give the title compound as a colorless liquid (yield 99%).

[0177] Synthesis Example 24 Synthesis of (1S,2R,3R,4S)-2-(1-ethoxyethoxy)-1-isopropyl-3-[(2-methoxybenzyl)oxy]-4-methyl-7-oxabicyclo[2.2.1]heptane(1-173) The same reaction and treatment were carried out as in Synthesis Example 22, except that 2-Methoxybenzyl bromide was used instead of 2-Chlorobenzyl bromide, to give the title compound as a colorless liquid (yield 83%).

[0178] Synthesis Example 25 Synthesis of (1S,2R,3R,4S)-2-(1-ethoxyethoxy)-3-[(2-fluorobenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptane(1-175) The same reaction and treatment were carried out as in Synthesis Example 22, except that 2-fluorobenzyl bromide was used instead of 2-chlorobenzyl bromide, to give the title compound as a colorless liquid (yield 85%).

[0179] Synthesis Example 26 Synthesis of (1S,2R,3R,4S)-2-[(2,3-difluorobenzyl)oxy]-3-(1-ethoxyethoxy)-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]heptane(1-179) The same reaction and treatment were carried out as in Synthesis Example 22, except that 2,3-difluorobenzyl bromide was used instead of 2-chlorobenzyl bromide, to give the title compound as a colorless liquid (yield 96%).

[0180] Synthesis Example 27 Synthesis of (1S,2R,3R,4S)-2-[(2,4-difluorobenzyl)oxy]-3-(1-ethoxyethoxy)-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]heptane(1-181) The same reaction and treatment were carried out as in Synthesis Example 22, except that 2,4-difluorobenzyl bromide was used instead of 2-chlorobenzyl bromide, to give the title compound (yield 83%) as a colorless liquid.

[0181] Synthesis Example 28 Synthesis of (1S,2R,3R,4S)-2-[(2,5-difluorobenzyl)oxy]-3-(1-ethoxyethoxy)-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]heptane(1-183) The same reaction and treatment were carried out as in Synthesis Example 22, except that 2,5-difluorobenzyl bromide was used instead of 2-chlorobenzyl bromide, to give the title compound as a colorless liquid (yield 92%).

[0182] Synthesis Example 29 Synthesis of (1S,2R,3R,4S)-2-[(2,6-difluorobenzyl)oxy]-3-(1-ethoxyethoxy)-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]heptane(1-185) The same reaction and treatment were carried out as in Synthesis Example 22, except that 2,6-Difluorobenzyl bromide was used instead of 2-Chlorobenzyl bromide, to give the title compound (yield 91%) as a colorless liquid.

[0183] Synthesis Example 30 Synthesis of (1S,2R,3R,4S)-2-[(3,5-difluorobenzyl)oxy]-3-(1-ethoxyethoxy)-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]heptane(1-187) The same reaction and treatment were carried out as in Synthesis Example 22, except that 3,5-difluorobenzyl bromide was used instead of 2-chlorobenzyl bromide, to give the title compound (yield 99%) as a colorless liquid.

[0184] Synthesis Example 31 Synthesis of (1S,2R,3R,4S)-2-[(2,6-dichlorobenzyl)oxy]-3-(1-ethoxyethoxy)-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]heptane(1-189) The same reaction and treatment were carried out as in Synthesis Example 22, except that 2,6-Dichlorobenzyl bromide was used instead of 2-Chlorobenzyl bromide, to give the title compound as a colorless liquid (yield 99%).

[0185] Synthesis Example 32 Synthesis of (1S,2R,3R,4S)-2-(1-ethoxyethoxy)-1-isopropyl-4-methyl-3-[[2-(trifluoromethyl)benzyl]oxy]-7-oxabicyclo[2.2.1]heptane(1-192) The same reaction and treatment were carried out as in Synthesis Example 22, except that 2-trifluoromethylbenzyl bromide was used in place of 2-chlorobenzyl bromide, to give the title compound as a colorless liquid (yield 99%).

[0186] Synthesis Example 33 Synthesis of (1R,2S,3S,4R)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-ol(1-62) p-Toluenesulfonic acid monohydrate (111 mg, 0.585 mmol) was added to a solution of (1S,2S,3R,6S)-6-isopropyl-3-methyl-2-[(2-methylbenzyl)oxy]-7-oxabicyclo[4.1.0]heptan-3-ol (170 mg, 0.585 mmol) in tetrahydrofuran (10 mL) and stirred at room temperature for 8 hours. Saturated aqueous sodium bicarbonate was poured into the reaction mixture, which was then extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane) to give the title compound (153 mg, 90%) as a colorless liquid.

[0187] Synthesis Example 34 Synthesis of (1S,2S,3R,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-ol(1-61) p-Toluenesulfonic acid monohydrate (477 mg, 2.77 mmol) was added to a solution of (1S,2R,3S,6S)-6-isopropyl-3-methyl-2-[(2-methylbenzyl)oxy]-7-oxabicyclo[4.1.0]heptan-3-ol (800 mg, 2.77 mmol) in tetrahydrofuran (28 mL) and stirred at room temperature for 8 hours and 20 minutes. Saturated aqueous sodium bicarbonate solution was poured into the reaction mixture, which was then extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane) to give the title compound (441 mg, 55%) as a colorless liquid.

[0188] Synthesis Example 35 Synthesis of (1R,2S,3S,4R)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-yl methanesulfonate (1-225) To a solution of (1R,2S,3S,4R)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-ol (114 mg, 0.392 mmol) in tetrahydrofuran (4 mL), triethylamine (0.099 mL, 0.71 mmol) and chloromethanesulfonic acid (0.033 mL, 0.43 mmol) were added and stirred for 14 hours and 30 minutes. Water was poured into the reaction mixture, which was then extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane) to give the title compound (55 mg, 77%) as a colorless liquid.

[0189] Synthesis Example 36 Synthesis of (1S,3R,4S)-1-isopropyl-2,4-dimethyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-ol(1-247) To a solution (6 mL) of (1S,3S,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-one (154 mg, 0.534 mmol) in tetrahydrofuran, MeLi (1.09 M in EtO, 0.98 mL, 1.1 mmol) was added and stirred at room temperature for 1 hour. Saturated aqueous ammonium chloride solution was poured into the reaction mixture, which was then extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane) to give the title compound (89.3 mg, 55%) as a colorless liquid.

[0190] Synthesis Example 37 Synthesis of (1S,3R,4S)-1-Isopropyl-3-[(2-methoxybenzyl)oxy]-2,4-dimethyl-7-oxabicyclo[2.2.1]heptan-2-ol(1-250) Sodium hydride (31.8 mg, 55% dispersion in mineral oil, 0.728 mmol) was added to a solution of (1S,3R,4S)-1-isopropyl-2,4-dimethyl-7-oxabicyclo[2.2.1]heptane-2,3-diol (72.9 mg, 0.364 mmol) in dimethylformamide (3.6 mL) and stirred at 0°C for 1 hour. 1-(iodomethyl)-2-methoxybenzene (90.3 mg, 0.364 mmol) was added to the reaction mixture and stirred at room temperature for 6 hours. Saturated aqueous ammonium chloride solution was poured into the reaction mixture, which was then extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane) to give the title compound (50.1 mg, 43%) as a colorless liquid.

[0191] Synthesis Example 38 Synthesis of (1S,3R,4S)-3-[(2-fluorobenzyl)oxy]-1-isopropyl-2,4-dimethyl-7-oxabicyclo[2.2.1]heptan-2-ol(1-252) The same reaction and treatment were carried out as in Synthesis Example 37, except that 2-Fluorobenzyl bromide was used instead of 1-(iodomethyl)-2-methoxybenzene, to give the title compound as a colorless liquid (yield 67%).

[0192] Synthesis Example 39 Synthesis of (1S,3R,4S)-3-[(2-chlorobenzyl)oxy]-1-isopropyl-2,4-dimethyl-7-oxabicyclo[2.2.1]heptan-2-ol(1-254) The same reaction and treatment were carried out as in Synthesis Example 37, except that 2-chlorobenzyl bromide was used instead of 1-(iodomethyl)-2-methoxybenzene, to give the title compound as a colorless liquid (yield 68%).

[0193] Synthesis Example 40 Synthesis of (1S,3R,4S)-3-[(2,6-difluorobenzyl)oxy]-1-isopropyl-2,4-dimethyl-7-oxabicyclo[2.2.1]heptan-2-ol(1-256) The same reaction and treatment were carried out as in Synthesis Example 37, except that 2,6-Difluorobenzyl bromide was used instead of 1-(iodomethyl)-2-methoxybenzene, to give the title compound as a colorless liquid (yield 22%).

[0194] Synthesis Example 41 Synthesis of (1S,3R,4S)-3-[(2,6-dichlorobenzyl)oxy]-1-isopropyl-2,4-dimethyl-7-oxabicyclo[2.2.1]heptan-2-ol(1-258) The same reaction and treatment were carried out as in Synthesis Example 37, except that 2,6-Dichlorobenzyl bromide was used instead of 1-(iodomethyl)-2-methoxybenzene, to give the title compound as a colorless liquid (yield 83%).

[0195] Synthesis Example 42 Synthesis of (1S,3R,4S)-1-isopropyl-2,4-dimethyl-3-[[2-(trifluoromethyl)benzyl]oxy]-7-oxabicyclo[2.2.1]heptan-2-ol(1-261) The same reaction and treatment were carried out as in Synthesis Example 37, except that 2-trifluorolmethylbenzyl bromide was used instead of 1-(iodomethyl)-2-methoxybenzene, to give the title compound as a colorless liquid (yield 78%).

[0196] Synthesis Example 43 Synthesis of (1S,3R,4S)-1-isopropyl-2,4-dimethyl-3-[[2-(trifluoromethoxy)benzyl]oxy]-7-oxabicyclo[2.2.1]heptan-2-ol(1-263) The same reaction and treatment were carried out as in Synthesis Example 37, except that 2-trifluorolmethoxybenzyl bromide was used instead of 1-(iodomethyl)-2-methoxybenzene, to give the title compound as a colorless liquid (yield 79%).

[0197] Synthesis Example 44 Synthesis of (1S,3R,4S)-2-ethyl-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-ol(1-266) Sodium hydride (11.2 mg, 55% dispersion in mineral oil, 0.257 mmol) was added to a solution of (1S,3R,4S)-2-ethyl-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptane-2,3-diol (50.1 mg, 0.234 mmol) in dimethylformamide (2.3 mL) and stirred at 0°C for 1 hour. 2-Methylbenzyl bromide (0.031 mL, 0.234 mmol) was added to the reaction mixture and stirred at room temperature for 2 hours. Saturated aqueous ammonium chloride solution was poured into the reaction mixture, which was then extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane) to give the title compound (31.3 mg, 46%) as a colorless liquid.

[0198] Synthesis Example 45 Synthesis of (1S,3R,4S)-3-(benzyloxy)-2-butyl-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-ol(1-273) To a solution (10 mL) of (1S,3S,4S)-3-(benzyloxy)-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-one (250 mg, 0.911 mmol) in tetrahydrofuran, n-butyllithium (1.58 M hexane solution, 0.69 mL, 1.1 mmol) was added and stirred at room temperature for 1 hour. Saturated aqueous ammonium chloride solution was poured into the reaction mixture, which was then extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane) to give the title compound (126 mg, 43%) as a colorless liquid.

[0199] Synthesis Example 46 Synthesis of (1S,3R,4S)-2-butyl-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-ol(1-275) In Synthesis Example 44, (1S,3R,4S)-2-butyl-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptane-2,3-diol was used instead of (1S,3R,4S)-2-ethyl-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptane-2,3-diol, and the same reaction and treatment were carried out to obtain the title compound (yield 46%) as a colorless liquid.

[0200] Synthesis Example 47 Synthesis of (1S,3R,4S)-1-isopropyl-2,4-dimethyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptane(1-73) Sodium hydride (55% dispersion in mineral oil, 33.0 mg, 0.756 mmol) was added to a solution of (1S,2R,4S)-4-isopropyl-1,3-dimethyl-7-oxabicyclo[2.2.1]heptan-2-ol (69.6 mg, 0.378 mmol) in dimethylformamide (3.8 mL) and stirred at 0°C for 1 hour. 2-Methylbenzyl bromide (0.051 mL, 0.38 mmol) was added to the reaction mixture and stirred at room temperature for 18 hours. Saturated aqueous ammonium chloride solution was poured into the reaction mixture, which was then extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane) to give the title compound (52.2 mg, 48%) as a colorless liquid.

[0201] Synthesis Example 48 Synthesis of (1S,3R,4S)-1-isopropyl-3-[(2-methoxybenzyl)oxy]-2,4-dimethyl-7-oxabicyclo[2.2.1]heptane(1-80) The same reaction and treatment were carried out as in Synthesis Example 44, except that 1-(iodomethyl)-2-methoxybenzene was used instead of 2-methylbenzyl bromide, to give the title compound (yield 50%) as a colorless liquid.

[0202] Synthesis Example 49 Synthesis of (1S,2R,4S)-2-[(2-fluorobenzyl)oxy]-4-isopropyl-1,3-dimethyl-7-oxabicyclo[2.2.1]heptane (1-82) The same reaction and treatment were carried out as in Synthesis Example 44, except that 2-fluorolbenzyl bromide was used instead of 2-methylbenzyl bromide, to give the title compound as a colorless liquid (yield 59%).

[0203] Synthesis Example 50 Synthesis of (1S,2R,4S)-2-[(2,3-difluorobenzyl)oxy]-4-isopropyl-1,3-dimethyl-7-oxabicyclo[2.2.1]heptane (1-95) The same reaction and treatment were carried out as in Synthesis Example 44, except that 2,3-Difluorolbenzyl bromide was used instead of 2-Methylbenzyl bromide, to give the title compound as a colorless liquid (yield 56%).

[0204] Synthesis Example 51 Synthesis of (1S,2R,4S)-2-[(2,4-difluorobenzyl)oxy]-4-isopropyl-1,3-dimethyl-7-oxabicyclo[2.2.1]heptane (1-97) The same reaction and treatment were carried out as in Synthesis Example 44, except that 2,4-Difluorolbenzyl bromide was used in place of 2-Methylbenzyl bromide, to give the title compound as a colorless liquid (yield 53%).

[0205] Synthesis Example 52 Synthesis of (1S,2R,4S)-2-[(2,5-difluorobenzyl)oxy]-4-isopropyl-1,3-dimethyl-7-oxabicyclo[2.2.1]heptane (1-99) The same reaction and treatment were carried out as in Synthesis Example 44, except that 2,5-Difluorolbenzyl bromide was used instead of 2-Methylbenzyl bromide, to give the title compound as a colorless liquid (yield 45%).

[0206] Synthesis Example 53 Synthesis of (1S,2R,4S)-2-[(2,6-difluorobenzyl)oxy]-4-isopropyl-1,3-dimethyl-7-oxabicyclo[2.2.1]heptane (1-101) The same reaction and treatment were carried out as in Synthesis Example 44, except that 2,6-Difluorolbenzyl bromide was used instead of 2-Methylbenzyl bromide, to give the title compound as a colorless liquid (yield 44%).

[0207] Synthesis Example 54 Synthesis of (1S,2R,4S)-2-[(3,5-difluorobenzyl)oxy]-4-isopropyl-1,3-dimethyl-7-oxabicyclo[2.2.1]heptane (1-107) The same reaction and treatment were carried out as in Synthesis Example 44, except that 3,5-Difluorolbenzyl bromide was used instead of 2-Methylbenzyl bromide, to give the title compound (yield 18%) as a colorless liquid.

[0208] Synthesis Example 55 Synthesis of (1S,2R,4S)-2-[(2-chlorobenzyl)oxy]-4-isopropyl-1,3-dimethyl-7-oxabicyclo[2.2.1]heptane (1-88) The same reaction and treatment were carried out as in Synthesis Example 44, except that 2-chlorobenzyl bromide was used instead of 2-methylbenzyl bromide, to give the title compound as a colorless liquid (yield 69%).

[0209] Synthesis Example 56 Synthesis of (1S,3S,4S)-2-bromo-2-(bromomethyl)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptane(1-283) A solution of bromine (0.0089 mL, 0.17 mmol) in dichloromethane (1 mL) was added to a solution of (1S,3R,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-2-methylene-7-oxabicyclo[2.2.1]heptane (45.1 mg, 0.157 mmol) in dichloromethane (2 mL) at -78 °C, and the mixture was stirred at -78 °C for 1 hour and 30 minutes. Saturated aqueous sodium thiosulfate was poured into the reaction mixture, which was then extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane) to give the title compound (37.8 mg, 54%) as a colorless liquid.

[0210] Synthesis Example 57 Synthesis of (1S,2R,3S,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxaspiro[bicyclo[2.2.1]heptane-2,2'-oxirane](1-291) 2-Chloroperbenzoic acid (66.2 mg, 0.269 mmol) was added to a dichloromethane solution (2 mL) of (1S,3R,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-2-methylene-7-oxabicyclo[2.2.1]heptane (50.0 mg, 0.175 mmol) and stirred at room temperature for 3 days. Saturated aqueous sodium bicarbonate was poured into the reaction mixture, which was then extracted with dichloromethane. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane) to yield the title compound (39.1 mg, 71%) as a colorless liquid.

[0211] Synthesis Example 58 Synthesis of (1S,3R,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-2-methylene-7-oxabicyclo[2.2.1]heptane(2-72) Sodium hydride (55% dispersion in mineral oil, 29.7 mg, 0.681 mmol) was added to a solution of (1S,2R,4S)-4-isopropyl-1-methyl-3-methylene-7-oxabicyclo[2.2.1]heptan-2-ol (82.8 mg, 0.454 mmol) in dimethylformamide (4.5 mL) and stirred at 0°C for 1 hour. 2-Methylbenzyl bromide (0.061 mL, 0.46 mmol) was added to the reaction mixture and stirred at room temperature for 12 hours. Saturated aqueous ammonium chloride solution was poured into the reaction mixture, which was then extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane) to give the title compound (46.4 mg, 36%) as a colorless liquid.

[0212] Synthesis Example 59 Synthesis of (1S,3R,4S)-1-isopropyl-4-methyl-3-[(3-methylbenzyl)oxy]-2-methylene-7-oxabicyclo[2.2.1]heptane(2-74) The same reaction and treatment were carried out as in Synthesis Example 58, except that 3-methylbenzyl bromide was used instead of 2-methylbenzyl bromide, to give the title compound as a colorless liquid (yield 86%).

[0213] Synthesis Example 60 Synthesis of (1S,3R,4S)-1-isopropyl-4-methyl-3-[(4-methylbenzyl)oxy]-2-methylene-7-oxabicyclo[2.2.1]heptane(2-76) The same reaction and treatment were carried out as in Synthesis Example 58, except that 4-methylbenzyl chloride was used instead of 2-methylbenzyl bromide, to give the title compound as a colorless liquid (yield 91%).

[0214] Synthesis Example 61 Synthesis of (1S,2R,4S)-2-[(2,6-dimethylbenzyl)oxy]-4-isopropyl-1-methyl-3-methylene-7-oxabicyclo[2.2.1]heptane(2-78) The same reaction and treatment were carried out as in Synthesis Example 58, except that 2,6-dimethylbenzyl chloride was used in place of 2-methylbenzyl bromide, to give the title compound as a colorless liquid (yield 94%).

[0215] Synthesis Example 62 Synthesis of (1S,3R,4S)-1-isopropyl-4-methyl-2-methylene-3-[(2,4,6-trimethylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptane(2-80) The same reaction and treatment were carried out as in Synthesis Example 58, except that 2,4,6-trimethylbenzyl chloride was used instead of 2-methylbenzyl bromide, to give the title compound as a colorless liquid (yield 99%).

[0216] Synthesis Example 63 Synthesis of (1S,3R,4S)-1-isopropyl-3-[(2-methoxybenzyl)oxy]-4-methyl-2-methylene-7-oxabicyclo[2.2.1]heptane(2-82) The same reaction and treatment were carried out as in Synthesis Example 58, except that 2-Methoxylbenzyl iodide was used instead of 2-Methylbenzyl bromide, to give the title compound as a colorless liquid (yield 89%).

[0217] Synthesis Example 64 Synthesis of (1S,3R,4S)-1-isopropyl-3-[(3-methoxybenzyl)oxy]-4-methyl-2-methylene-7-oxabicyclo[2.2.1]heptane(2-84) The same reaction and treatment were carried out as in Synthesis Example 58, except that 3-Methoxylbenzyl bromide was used instead of 2-Methylbenzyl bromide, to give the title compound as a colorless liquid (yield 91%).

[0218] Synthesis Example 65 Synthesis of (1S,3R,4S)-1-isopropyl-3-[(4-methoxybenzyl)oxy]-4-methyl-2-methylene-7-oxabicyclo[2.2.1]heptane(2-86) The same reaction and treatment were carried out as in Synthesis Example 58, except that 4-Methoxylbenzyl bromide was used instead of 2-Methylbenzyl bromide, to give the title compound as a colorless liquid (yield 100%).

[0219] Synthesis Example 66 Synthesis of (1S,2R,4S)-2-[(2-fluorobenzyl)oxy]-4-isopropyl-1-methyl-3-methylene-7-oxabicyclo[2.2.1]heptane(2-88) The same reaction and treatment were carried out as in Synthesis Example 58, except that 2-fluoroobenzyl bromide was used in place of 2-methylbenzyl bromide, to give the title compound as a colorless liquid (yield 73%).

[0220] Synthesis Example 67 Synthesis of (1S,2R,4S)-2-[(3-fluorobenzyl)oxy]-4-isopropyl-1-methyl-3-methylene-7-oxabicyclo[2.2.1]heptane(2-90) The same reaction and treatment were carried out as in Synthesis Example 58, except that 3-Fluorobenzyl bromide was used instead of 2-Methylbenzyl bromide, to give the title compound as a colorless liquid (yield 73%).

[0221] Synthesis Example 68 Synthesis of (1S,2R,4S)-2-[(4-fluorobenzyl)oxy]-4-isopropyl-1-methyl-3-methylene-7-oxabicyclo[2.2.1]heptane(2-92) The same reaction and treatment were carried out as in Synthesis Example 58, except that 4-Fluorobenzyl bromide was used instead of 2-Methylbenzyl bromide, to give the title compound as a colorless liquid (yield 67%).

[0222] Synthesis Example 69 Synthesis of (1S,2R,4S)-2-[(2-chlorobenzyl)oxy]-4-isopropyl-1-methyl-3-methylene-7-oxabicyclo[2.2.1]heptane(2-94) The same reaction and treatment were carried out as in Synthesis Example 58, except that 2-chlorobenzyl bromide was used in place of 2-methylbenzyl bromide, to give the title compound as a colorless liquid (yield 40%).

[0223] Synthesis Example 70 Synthesis of (1S,2R,4S)-2-[(2,3-difluorobenzyl)oxy]-4-isopropyl-1-methyl-3-methylene-7-oxabicyclo[2.2.1]heptane(2-98) The same reaction and treatment were carried out as in Synthesis Example 58, except that 2,3-difluorolbenzyl bromide was used in place of 2-methylbenzyl bromide, to give the title compound as a colorless liquid (yield 69%).

[0224] Synthesis Example 71 Synthesis of (1S,2R,4S)-2-[(2,4-difluorobenzyl)oxy]-4-isopropyl-1-methyl-3-methylene-7-oxabicyclo[2.2.1]heptane(2-100) The same reaction and treatment were carried out as in Synthesis Example 58, except that 2,4-difluorolbenzyl bromide was used in place of 2-methylbenzyl bromide, to give the title compound as a colorless liquid (yield 68%).

[0225] Synthesis Example 72 Synthesis of (1S,2R,4S)-2-[(2,5-difluorobenzyl)oxy]-4-isopropyl-1-methyl-3-methylene-7-oxabicyclo[2.2.1]heptane(2-102) The same reaction and treatment were carried out as in Synthesis Example 58, except that 2,5-difluorolbenzyl bromide was used in place of 2-methylbenzyl bromide, to give the title compound as a colorless liquid (yield 71%).

[0226] Synthesis Example 73 Synthesis of (1S,2R,4S)-2-[(2,6-difluorobenzyl)oxy]-4-isopropyl-1-methyl-3-methylene-7-oxabicyclo[2.2.1]heptane(2-104) The same reaction and treatment were carried out as in Synthesis Example 58, except that 2,6-difluorolbenzyl bromide was used in place of 2-methylbenzyl bromide, to give the title compound as a colorless liquid (yield 98%).

[0227] Synthesis Example 74 Synthesis of (1S,2R,4S)-2-[(3,5-difluorobenzyl)oxy]-4-isopropyl-1-methyl-3-methylene-7-oxabicyclo[2.2.1]heptane(2-106) The same reaction and treatment were carried out as in Synthesis Example 58, except that 3,5-difluorolbenzyl bromide was used instead of 2-methylbenzyl bromide, to give the title compound as a colorless liquid (yield 70%).

[0228] Synthesis Example 75 Synthesis of (1S,2R,4S)-2-[(2,6-dichlorobenzyl)oxy]-4-isopropyl-1-methyl-3-methylene-7-oxabicyclo[2.2.1]heptane(2-110) The same reaction and treatment were carried out as in Synthesis Example 58, except that 2,6-dichlorolbenzyl bromide was used in place of 2-methylbenzyl bromide, to give the title compound as a colorless liquid (yield 94%).

[0229] Synthesis Example 76 Synthesis of (1S,2R,4S)-2-[(2-chloro-6-fluorobenzyl)oxy]-4-isopropyl-1-methyl-3-methylene-7-oxabicyclo[2.2.1]heptane(2-112) The same reaction and treatment were carried out as in Synthesis Example 58, except that 2-chloro-6-fluorolbenzyl bromide was used in place of 2-methylbenzyl bromide, to give the title compound as a colorless liquid (yield 67%).

[0230] Synthesis Example 77 Synthesis of (1S,3R,4S)-1-isopropyl-4-methyl-2-methylene-3-[[2-(trifluoromethyl)benzyl]oxy]-7-oxabicyclo[2.2.1]heptane(2-116) The same reaction and treatment were carried out as in Synthesis Example 58, except that 2-(Trifluoromethyl)benzyl bromide was used in place of 2-methylbenzyl bromide, to give the title compound as a colorless liquid (yield 96%).

[0231] Synthesis Example 78 Synthesis of (1S,3R,4S)-1-isopropyl-4-methyl-2-methylene-3-[[3-(trifluoromethyl)benzyl]oxy]-7-oxabicyclo[2.2.1]heptane(2-118) The same reaction and treatment were carried out as in Synthesis Example 58, except that 3-(Trifluoromethyl)benzyl bromide was used in place of 2-methylbenzyl bromide, to give the title compound as a colorless liquid (yield 83%).

[0232] Synthesis Example 79 Synthesis of (1S,3R,4S)-1-isopropyl-4-methyl-2-methylene-3-[[4-(trifluoromethyl)benzyl]oxy]-7-oxabicyclo[2.2.1]heptane(2-120) The same reaction and treatment were carried out as in Synthesis Example 58, except that 4-(Trifluoromethyl)benzyl bromide was used in place of 2-methylbenzyl bromide, to give the title compound as a colorless liquid (yield 82%).

[0233] Synthesis Example 80 Synthesis of (1S,2R,4S)-2-[[2-fluoro-6-(trifluoromethyl)benzyl]oxy]-4-isopropyl-1-methyl-3-methylene-7-oxabicyclo[2.2.1]heptane(2-122) The same reaction and treatment were carried out as in Synthesis Example 58, except that 2-Fluoro-6-(trifluoromethyl)-benzyl bromide was used instead of 2-Methylbenzyl bromide, to give the title compound as a colorless liquid (yield 96%).

[0234] Synthesis Example 81 Synthesis of (1S,3R,4S)-1-isopropyl-4-methyl-2-methylene-3-[[2-(trifluoromethoxy)benzyl]oxy]-7-oxabicyclo[2.2.1]heptane(2-124) The same reaction and treatment were carried out as in Synthesis Example 58, except that 2-(Trifluoromethoxy)benzyl bromide was used in place of 2-methylbenzyl bromide, to give the title compound as a colorless liquid (yield 69%).

[0235] Synthesis Example 82 Synthesis of (1S,3R,4S)-1-isopropyl-4-methyl-2-methylene-3-[[3-(trifluoromethoxy)benzyl]oxy]-7-oxabicyclo[2.2.1]heptane(2-126) The same reaction and treatment were carried out as in Synthesis Example 58, except that 3-(Trifluoromethoxy)benzyl bromide was used instead of 2-methylbenzyl bromide, to give the title compound as a colorless liquid (yield 91%).

[0236] Synthesis Example 83 Synthesis of (1S,3R,4S)-1-isopropyl-4-methyl-2-methylene-3-[[4-(trifluoromethoxy)benzyl]oxy]-7-oxabicyclo[2.2.1]heptane(2-128) The same reaction and treatment were carried out as in Synthesis Example 58, except that 4-(Trifluoromethoxy)benzyl bromide was used instead of 2-methylbenzyl bromide, to give the title compound as a colorless liquid (yield 84%).

[0237] Synthesis Example 84 Synthesis of (1S,3S,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-one(2-3) Pyridinium chlorochromate (1.07 g, 4.98 mmol) and Celite (1.61 g) were added to a dichloromethane solution (11 mL) of (1S,2R,3R,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-ol (964 mg, 3.32 mmol), and the mixture was stirred at room temperature for 11 hours. The reaction mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane) to give the title compound (637 mg, 67%) as a colorless liquid.

[0238] Synthesis Example 85 Synthesis of (1S,3S,4S)-3-(benzyloxy)-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-one(2-1) In Synthesis Example 84, (1S,2R,3R,4S)-3-(benzyloxy)-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-ol was used instead of (1S,2R,3R,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy)-7-oxabicyclo[2.2.1]heptan-2-ol, and the same reaction and treatment were carried out to obtain the title compound (yield 88%) as a colorless liquid.

[0239] Synthesis Example 86 Synthesis of (1S,3S,4S)-3-[(2,6-dimethylbenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-one(2-5) In Synthesis Example 84, (1S,2R,3R,4S)-3-[(2,6-dimethylbenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-ol was used instead of (1S,2R,3R,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-ol, and the same reaction and treatment were carried out to obtain the title compound (yield 97%) as a colorless liquid.

[0240] Synthesis Example 87 Synthesis of (1S,3S,4S)-1-isopropyl-3-[(2-methoxybenzyl)oxy]-4-methyl-7-oxabicyclo[2.2.1]heptan-2-one(2-7) In Synthesis Example 84, (1S,2R,3R,4S)-1-isopropyl-3-[(2-methoxybenzyl)oxy]-4-methyl-7-oxabicyclo[2.2.1]heptan-2-ol was used instead of (1S,2R,3R,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-ol, and the same reaction and treatment were carried out to obtain the title compound (yield 86%) as a colorless liquid.

[0241] Synthesis Example 88 Synthesis of (1S,3S,4S)-3-[(2-fluorobenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-one(2-9) In Synthesis Example 84, (1S,2R,3R,4S)-3-[(2-fluorobenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-ol was used instead of (1S,2R,3R,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-ol, and the same reaction and treatment were carried out to obtain the title compound (yield 94%) as a colorless liquid.

[0242] Synthesis Example 89 Synthesis of (1S,3S,4S)-3-[(2-chlorobenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-one(2-11) In Synthesis Example 84, (1S,2R,3R,4S)-3-[(2-chlorobenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-ol was used instead of (1S,2R,3R,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-ol, and the same reaction and treatment were carried out to obtain the title compound (yield 95%) as a colorless liquid.

[0243] Synthesis Example 90 Synthesis of (1S,3S,4S)-3-[(2,3-difluorobenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-one(2-14) In Synthesis Example 84, (1S,2R,3R,4S)-3-[(2,3-difluorobenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-ol was used instead of (1S,2R,3R,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-ol, and the same reaction and treatment were carried out to obtain the title compound (yield 97%) as a colorless liquid.

[0244] Synthesis Example 91 Synthesis of (1S,3S,4S)-3-[(2,4-difluorobenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-one(2-16) In Synthesis Example 84, (1S,2R,3R,4S)-3-[(2,4-difluorobenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-ol was used instead of (1S,2R,3R,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-ol, and the same reaction and treatment were carried out to obtain the title compound (yield 95%) as a colorless liquid.

[0245] Synthesis Example 92 Synthesis of (1S,3S,4S)-3-[(2,5-difluorobenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-one(2-18) In Synthesis Example 84, (1S,2R,3R,4S)-3-[(2,5-difluorobenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-ol was used instead of (1S,2R,3R,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-ol, and the same reaction and treatment were carried out to obtain the title compound (yield 100%) as a colorless liquid.

[0246] Synthesis Example 93 Synthesis of (1S,3S,4S)-3-[(2,6-difluorobenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-one(2-20) In Synthesis Example 84, (1S,2R,3R,4S)-3-[(2,6-difluorobenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-ol was used instead of (1S,2R,3R,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-ol, and the same reaction and treatment were carried out to obtain the title compound (yield 95%) as a colorless liquid.

[0247] Synthesis Example 94 Synthesis of (1S,3S,4S)-3-[(3,5-difluorobenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-one(2-22) In Synthesis Example 84, (1S,2R,3R,4S)-3-[(3,5-difluorobenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-ol was used instead of (1S,2R,3R,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-ol, and the same reaction and treatment were carried out to obtain the title compound (yield 91%) as a colorless liquid.

[0248] Synthesis Example 95 Synthesis of (1S,3S,4S)-1-isopropyl-4-methyl-3-[(perfluorophenyl)methoxy]-7-oxabicyclo[2.2.1]heptan-2-one(2-24) In Synthesis Example 84, (1S,2R,3R,4S)-1-isopropyl-4-methyl-3-[(perfluorophenyl)methoxy]-7-oxabicyclo[2.2.1]heptan-2-ol was used instead of (1S,2R,3R,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-ol, and the same reaction and treatment were carried out to obtain the title compound (yield 82%) as a colorless liquid.

[0249] Synthesis Example 96 Synthesis of (1S,3S,4S)-3-[(2,6-dichlorobenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-one(2-26) In Synthesis Example 84, (1S,2R,3R,4S)-3-[(2,6-dichlorobenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-ol was used instead of (1S,2R,3R,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-ol, and the same reaction and treatment were carried out to obtain the title compound (yield 93%) as a colorless liquid.

[0250] Synthesis Example 97 Synthesis of (1S,3S,4S)-1-isopropyl-4-methyl-3-[[2-(trifluoromethyl)benzyl]oxy]-7-oxabicyclo[2.2.1]heptan-2-one(2-29) In Synthesis Example 84, (1S,2R,3R,4S)-1-isopropyl-4-methyl-3-[[2-(trifluoromethyl)benzyl]oxy]-7-oxabicyclo[2.2.1]heptan-2-ol was used instead of (1S,2R,3R,4S)-1-isopropyl-4-methyl-3-[[2-(trifluoromethyl)benzyl]oxy]-7-oxabicyclo[2.2.1]heptan-2-ol, and the same reaction and treatment were carried out to obtain the title compound (yield 92%) as a colorless liquid.

[0251] Synthesis Example 98 Synthesis of (1S,3R,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-one oxime(2-191) Hydroxylamine monohydrate (57.1 mg, 0.822 mmol) and sodium acetate (90.2 mg, 1.10 mmol) were added to a solution of (1S,3S,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-one (158 mg, 0.548 mmol) in ethanol (4 mL) and water (1 mL), and the mixture was stirred under reflux for 8 hours. The reaction mixture was extracted with ethyl acetate, and the extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane) to give the title compound (107 mg, 67%) as a colorless liquid.

[0252] Synthesis Example 99 Synthesis of (1S,3R,4S)-3-[(2,6-dimethylbenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-one oxime(2-193) In Synthesis Example 98, (1S,3S,4S)-3-[(2,6-dimethylbenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-one was used instead of (1S,3S,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-one, and the same reaction and treatment were carried out to obtain the title compound (yield 91%) as a colorless liquid.

[0253] Synthesis Example 100 Synthesis of (1S,3R,4S)-1-isopropyl-3-[(2-methoxybenzyl)oxy]-4-methyl-7-oxabicyclo[2.2.1]heptan-2-one oxime(2-195) In Synthesis Example 98, (1S,3S,4S)-1-isopropyl-3-[(2-methoxybenzyl)oxy]-4-methyl-7-oxabicyclo[2.2.1]heptan-2-one was used instead of (1S,3S,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-one, and the same reaction and treatment were carried out to obtain the title compound as a colorless liquid (yield 96%).

[0254] Synthesis Example 101 Synthesis of (1S,3R,4S)-3-[(2-fluorobenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-one oxime(2-197) In Synthesis Example 98, (1S,3S,4S)-3-[(2-fluorobenzyl)oxy)-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-one was used instead of (1S,3S,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-one, and the same reaction and treatment were carried out to obtain the title compound as a colorless liquid (yield 92%).

[0255] Synthesis Example 102 Synthesis of (1S,3R,4S)-3-[(2-chlorobenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-one oxime(2-199) In Synthesis Example 98, (1S,3S,4S)-3-[(2-chlorobenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-one was used instead of (1S,3S,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-one, and the same reaction and treatment were carried out to obtain the title compound (yield 98%) as a colorless liquid.

[0256] Synthesis Example 103 Synthesis of (1S,3R,4S)-3-[(2,3-difluorobenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-one oxime(2-201) In Synthesis Example 98, (1S,3S,4S)-3-[(2,3-difluorobenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-one was used instead of (1S,3S,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-one, and the same reaction and treatment were carried out to obtain the title compound (yield 98%) as a colorless liquid.

[0257] Synthesis Example 104 Synthesis of (1S,3R,4S)-3-[(2,4-difluorobenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-one oxime(2-203) In Synthesis Example 98, (1S,3S,4S)-3-[(2,4-difluorobenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-one was used instead of (1S,3S,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-one, and the same reaction and treatment were carried out to obtain the title compound (yield 98%) as a colorless liquid.

[0258] Synthesis Example 105 Synthesis of (1S,3R,4S)-3-[(2,5-difluorobenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-one oxime(2-205) In Synthesis Example 98, (1S,3S,4S)-3-[(2,5-difluorobenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-one was used instead of (1S,3S,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-one, and the same reaction and treatment were performed to obtain the title compound as a white solid (yield 100%).

[0259] Synthesis Example 106 Synthesis of (1S,3R,4S)-3-[(2,6-difluorobenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-one oxime(2-207) In Synthesis Example 98, (1S,3S,4S)-3-[(2,6-difluorobenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-one was used instead of (1S,3S,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-one, and the same reaction and treatment were carried out to obtain the title compound (yield 97%) as a colorless liquid.

[0260] Synthesis Example 107 Synthesis of (1S,3R,4S)-3-[(3,5-difluorobenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-one oxime(2-209) In Synthesis Example 98, (1S,3S,4S)-3-[(3,5-difluorobenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-one was used instead of (1S,3S,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-one, and the same reaction and treatment were performed to obtain the title compound as a white solid (yield 100%).

[0261] Synthesis Example 108 Synthesis of (1S,3R,4S)-1-isopropyl-4-methyl-3-[(perfluorophenyl)methoxy]-7-oxabicyclo[2.2.1]heptan-2-one oxime(2-211) In Synthesis Example 98, (1S,3S,4S)-1-isopropyl-4-methyl-3-[(perfluorophenyl)methoxy]-7-oxabicyclo[2.2.1]heptan-2-one was used instead of (1S,3S,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-one, and the same reaction and treatment were carried out to obtain the title compound (yield 99%) as a colorless liquid.

[0262] Synthesis Example 109 Synthesis of (1S,3R,4S)-3-[(2,6-dichlorobenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-one oxime(2-213) In Synthesis Example 98, (1S,3S,4S)-3-[(2,6-dichlorobenzyl)oxy]-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-one was used instead of (1S,3S,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-one, and the same reaction and treatment were carried out to obtain the title compound (yield 90%) as a colorless liquid.

[0263] Synthesis Example 110 Synthesis of (1S,3R,4S)-1-isopropyl-4-methyl-3-[[2-(trifluoromethyl)benzyl]oxy]-7-oxabicyclo[2.2.1]heptan-2-one oxime(2-216) In Synthesis Example 98, (1S,3S,4S)-1-isopropyl-4-methyl-3-[[2-(trifluoromethyl)benzyl]oxy]-7-oxabicyclo[2.2.1]heptan-2-one was used instead of (1S,3S,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-one, and the same reaction and treatment were carried out to obtain the title compound (yield 85%) as a colorless liquid.

[0264] Synthesis Example 111 Synthesis of (1S,3R,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-one O-methyl oxime(2-227) Methoxyamine hydrochloride (0.063 mL, 0.34 mmol) and pyridine (0.033 mL, 0.41 mmol) were added to a methanol solution (2.3 mL) of (1S,3S,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-one (64.7 mg, 0.226 mmol) and the mixture was stirred at room temperature for 21 hours and 30 minutes. Saturated brine was poured into the reaction mixture, which was then extracted with dichloromethane. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane) to give the title compound (63.8 mg, 89%) as a colorless liquid.

[0265] Synthesis Example 112 Synthesis of [(1S,3R,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-ylidene]hydrazine(2-240) A solution of (1S,3S,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-one (165 mg, 0.572 mmol) in ethanol (6 mL) was added with hydrazine monohydrate (0.11 mL, 2.3 mmol) and acetic acid (0.03 mL, 0.6 mmol), and the mixture was stirred under reflux for 2 hours and 30 minutes. The reaction mixture was concentrated under reduced pressure, and the concentrate was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane) to give the title compound (128 mg, 74%) as a colorless liquid.

[0266] Synthesis Example 113 Synthesis of 1-[(1S,3R,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-ylidene]-2-methylhydrazine(2-247) The same reaction and treatment were carried out as in Synthesis Example 112, except that methylhydrazine was used in place of hydrazine monohydrate, to give the title compound as a colorless liquid (yield: 51%).

[0267] Synthesis Example 114 Synthesis of 1-[(1S,3R,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-ylidene]-2-phenylhydrazine (2-261) The same reaction and treatment were carried out as in Synthesis Example 112, except that phenylhydrazine was used in place of hydrazine monohydrate, to give the title compound as a colorless liquid (yield 85%).

[0268] Synthesis Example 115 Synthesis of 2-[(1S,3R,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-ylidene]hydrazine-1-carboxamide (2-254) Semicarbazide hydrochloride (64.9 mg, 0.537 mmol) and sodium acetate (44.1 mg, 0.537 mmol) were added to a mixture of (1S,3S,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-one (155 mg, 0.537 mmol) in ethanol (3 mL) and water (3 mL), and the mixture was stirred under reflux for 24 hours. The reaction mixture was concentrated under reduced pressure, and the concentrate was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane) to give the title compound (110 mg, 59%) as a white solid.

[0269] Synthesis Example 116 Synthesis of (1S,2R,3R,4S)-3-((tert-butyldimethylsilyl)oxy)-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-ol p-Toluenesulfonic acid monohydrate (557 mg, 2.93 mmol) was added to a solution (29 mL) of (1R,2R,3S,6R)-2-((tert-butyldimethylsilyl)oxy)-6-isopropyl-3-methyl-7-oxabicyclo[4.1.0]heptan-3-ol (880 mg, 2.93 mmol) in tetrahydrofuran, and the mixture was stirred at room temperature for 2.5 hours. A saturated aqueous solution of sodium bicarbonate was poured into the reaction mixture, which was then extracted with dichloromethane. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane) to give the title compound (793 mg, 90%) as a colorless liquid. 1HNMR spectrum (CDCl3) δ0.08(s,3H),0.10(s,3H),0.92(s,9H),1.000(d,J=6.8Hz,3H),1.004(d,J=6.8Hz,3H ),1.29(s,3H),1.43-1.65(m,3H),2.01-2.12(m,2H),3.49(d,J=1.2Hz,1H),3.78(dt,J=4.4,1.6Hz,1H).

[0270] Synthesis Example 117 Synthesis of (1S,3S,4S)-3-((tert-butyldimethylsilyl)oxy)-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-one Pyridinium chlorochromate (756 mg, 3.51 mmol) and Celite (1.50 g) were added to a dichloromethane solution (23 mL) of (1S,2R,3R,4S)-3-((tert-butyldimethylsilyl)oxy)-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-ol (702 mg, 2.34 mmol), and the mixture was stirred at room temperature for 68 hours. The reaction mixture was filtered and then concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane) to give the title compound (666 mg, 96%) as a colorless liquid. 1 HNMR spectrum (CDCl3) δ0.11(s,3H),0.13(s,3H),0.90(s,9H),1.04(d,J=7.2Hz,3H),1.05(d,J=7.2H) z,3H),1.44(s,3H),1.53-1.67(m,2H),1.71-1.88(m,2H),2.14(sept,J=6.9Hz,1H),3.46(s,1H).

[0271] Synthesis Example 118 Synthesis of (1S,3R,4S)-3-((tert-butyldimethylsilyl)oxy)-1-isopropyl-2,4-dimethyl-7-oxabicyclo[2.2.1]heptan-2-ol Methyllithium (0.810 mL, 1.09 mol / L diethyl ether solution, 0.883 mmol) was added to a solution of (1S,3S,4S)-3-((tert-butyldimethylsilyl)oxy)-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-one (176 mg, 0.589 mmol) in tetrahydrofuran (6 mL), and the mixture was stirred at room temperature for 3 hours. Saturated aqueous ammonium chloride solution was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (extractant: ethyl acetate / n-hexane) to give the title compound (165 mg, 89%) as a colorless liquid. 1 HNMR spectrum (CDCl3) δ0.12(s,6H),0.95(s,9H),0.97(d,J=7.2Hz,3H),0.98(d,J=7.2Hz,3H),1. 29(s,3H),1.36(s,3H),1.43-1.68(m,4H),2.54(sept,J=7.2Hz,1H),3.36(s,1H),3.39(s,1H).

[0272] Synthesis Example 119 Synthesis of (1S,3R,4S)-1-isopropyl-2,4-dimethyl-7-oxabicyclo[2.2.1]heptane-2,3-diol Tetrabutylammonium fluoride (0.67 mL, 1 mol / L tetrahydrofuran solution, 0.67 mmol) was added to a tetrahydrofuran solution (2 mL) of (1S,3R,4S)-3-((tert-butyldimethylsilyl)oxy)-1-isopropyl-2,4-dimethyl-7-oxabicyclo[2.2.1]heptan-2-ol (161 mg, 0.512 mmol) and the mixture was stirred at room temperature for 14 hours and 30 minutes. Saturated aqueous ammonium chloride solution was poured into the reaction mixture, which was then extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (extractant: ethyl acetate / n-hexane) to give the title compound (100 mg, 98%) as a colorless liquid. 1 HNMR spectrum (CDCl3) δ0.98(d,J=7.2Hz,3H),0.99(d,J=7.2Hz,3H),1.35(s,3H),1.40(s,3H),1. 50-1.63(m,3H),1.65-1.74(m,1H),2.41(m,2H),2.70(d,J=6.8Hz,1H),3.34(d,J=6.8Hz,1H).

[0273] Synthesis Example 120 Synthesis of (tert-butyl(((1S,2R,4S)-4-isopropyl-1-methyl-3-methylene-7-oxabicyclo[2.2.1]heptan-2-yl)oxy)dimethylsilane To a solution of methyltriphenylphosphonium bromide (536 mg, 1.50 mmol) in tetrahydrofuran (5 mL), n-butyllithium (0.87 mL, 1.56 mol / L hexane solution, 1.4 mmol) was added and stirred at 0°C for 1 hour. (1S,3S,4S)-3-((tert-butyldimethylsilyl)oxy)-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-one (224 mg, 0.750 mmol) was added to the reaction mixture, and the mixture was stirred at 0°C for 3 hours. Saturated aqueous ammonium chloride solution was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane) to give the title compound as a colorless liquid (yield 207 mg, 93%). 1 HNMR spectrum (CDCl3) δ0.09(d,J=1.2Hz,6H),0.90(s,9H),1.06(d,J=6.8Hz,3H),1.09(d,J=6.8Hz,3H),1.37(s,3H),1.38 -1.49(m,2H),1.50-1.59(m,1H),1.77-1.85(m,1H),2.18(sept,J=6.8Hz,1H),3.94(s,1H),5.02(dd,J=3.0,1.0Hz,2H).

[0274] Synthesis Example 121 Synthesis of (1S,2R,4S)-4-isopropyl-1-methyl-3-methylene-7-oxabicyclo[2.2.1]heptan-2-ol Tetrabutylammonium fluoride (0.94 mL, a 1 mol / L tetrahydrofuran solution, 0.94 mmol) was added to a solution (3 mL) of (tert-butyl(((1S,2R,4S)-4-isopropyl-1-methyl-3-methylene-7-oxabicyclo[2.2.1]heptan-2-yl)oxy)dimethylsilane (214 mg, 0.722 mmol) in tetrahydrofuran, and the mixture was stirred at room temperature for 13 hours. A saturated aqueous solution of ammonium chloride was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (extractant: ethyl acetate / n-hexane) to give the title compound (123 mg, 93% yield) as a colorless liquid. 1 HNMR spectrum (CDCl3) δ1.07(d,J=6.8Hz,3H),1.10(d,J=6.8Hz,3H),1.43(s,3H),1.38-1.65(m,3H),1.79-1. 87(m,1H),2.18(sept,J=6.8Hz,1H),3.84(d,J=10.0Hz,1H),5.09(d,J=0.9Hz,1H),5.26(d,J=1.2Hz,1H).

[0275] Synthesis Example 122 Synthesis of (1S,2R,4S)-4-isopropyl-1,3-dimethyl-7-oxabicyclo[2.2.1]heptan-2-ol Palladium on carbon (67.8 mg, 55 wt% water) was added to a methanol solution (6 mL) of (1S,2R,4S)-4-isopropyl-1-methyl-3-methylene-7-oxabicyclo[2.2.1]heptan-2-ol (104 mg, 0.571 mmol), and the mixture was stirred at room temperature under a hydrogen atmosphere for 2 hours. The reaction mixture was filtered through Celite and then concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane) to give the title compound (88.0 mg, 84% yield) as a colorless liquid. 1 HNMR spectrum (CDCl3) δ0.87(d,J=6.8Hz,1.56H),0.91(d,J=6.8Hz,1.56H),0.97-1.02(m,4.44H),1.12(d,J=6.8Hz,1.44H),1.22-1.29(m,0.52H),1.36( s,1.56H),1.38(s,1.44H),1.40-1.62(m,2.04H),1.66-1.83(m,1.44H),1. 97-2.20(m,2H),3.20(d,J=3.2Hz,0.52H),3.75(dd,J=9.2,7.2Hz,0.48H).

[0276] Synthesis Example 123 Synthesis of tert-butyl(((1S,2R,3R,4S)-4-isopropyl-3-methoxy-1-methyl-7-oxabicyclo[2.2.1]heptan-2-yl)oxy)dimethylsilane Sodium hydride (55% dispersion in mineral oil, 40.4 mg, 0.927 mmol) was added to a solution of (1S,2R,3R,4S)-3-((tert-butyldimethylsilyl)oxy)-1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-ol (139 mg, 0.464 mmol) in tetrahydrofuran (5 mL) and stirred at 0°C for 1 hour. Iodomethane (0.173 mL, 2.78 mmol) was added to the reaction mixture and stirred at room temperature for 22 hours. Saturated aqueous ammonium chloride solution was poured into the reaction mixture, which was then extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane) to give the title compound (104 mg, 72% yield) as a colorless liquid. 1 HNMR spectrum (CDCl3) δ0.06(s,3H),0.10(s,3H),0.90(s,9H),0.960(d,J=6.8Hz,3H),0.964(d,J=6.8Hz,3H),1.26( s,3H),1.34-1.43(m,1H),1.46-1.58(m,2H),1.93-2.07(m,2H),3.30(s,1H),3.41(s,3H),3.53(d,J=1.2Hz,1H).

[0277] Synthesis Example 124 Synthesis of (1S,2R,3R,4S)-4-isopropyl-3-methoxy-1-methyl-7-oxabicyclo[2.2.1]heptan-2-ol Tetrabutylammonium fluoride (1.70 mL, 1 mol / L tetrahydrofuran solution, 1.70 mmol) was added to a solution of tert-butyl(((1S,2R,3R,4S)-4-isopropyl-3-methoxy-1-methyl-7-oxabicyclo[2.2.1]heptan-2-yl)oxy)dimethylsilane (410 mg, 1.30 mmol) in tetrahydrofuran (4 mL), and the mixture was stirred at room temperature for 22 hours and 30 minutes. Saturated aqueous ammonium chloride solution was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (extractant: ethyl acetate / n-hexane) to give the title compound as a colorless liquid (yield 231 mg, 88%). 1 HNMR spectrum (CDCl3) δ0.97(d,J=6.8Hz,3H),0.98(d,J=6.8Hz,3H),1.36(s,3H),1,42(tdd,J=11.8,5.7,1.5Hz,1H),1,5 4-1.66(m,2H),1.66(s,2H),1.72(d,J=9.6Hz,1H),1.98-2.08(m,2H),3.23(s,1H),3.43(s,3H),3.53(d,J=8.4Hz,1H).

[0278] Synthesis Example 125 Synthesis of (1S,2R,3R,4S)-4-isopropyl-1,3-dimethyl-7-oxabicyclo[2.2.1]heptan-2-ol and (1S,2R,3S,4S)-4-isopropyl-1,3-dimethyl-7-oxabicyclo[2.2.1]heptan-2-ol In Synthesis Example 122, purification was carried out by silica gel column chromatography (extractant: ethyl acetate / n-hexane) to obtain colorless liquid (1S,2R,3R,4S)-4-isopropyl-1,3-dimethyl-7-oxabicyclo[2.2.1]heptan-2-ol (yield 25%) and white solid (1S,2R,3S,4S)-4-isopropyl-1,3-dimethyl-7-oxabicyclo[2.2.1]heptan-2-ol (yield 43%). (1S,2R,3R,4S)-4-isopropyl-1,3-dimethyl-7-oxabicyclo[2.2.1]heptan-2-ol 1 HNMR spectrum (CDCl3) δ0.98(d,J=6.8Hz,3H),1.01(d,,J=6.8Hz,3H),1.12(d,J=7.2Hz,3H),1.23-1.28(m,1H),1.36 (s,3H),1.40-1.49(m,2H),1.53-1.63(m,1H),1.74-1.81(m,1H),1.99-2.06(m,1H),3.20(dd,J=9.6,2.8Hz,1H). (1S,2R,3S,4S)-4-isopropyl-1,3-dimethyl-7-oxabicyclo[2.2.1]heptan-2-ol 1 HNMR spectrum (CDCl3) δ0.88(d,J=6.8Hz,3H),0.91(d,J=6.8Hz,3H),1.00(d,J=6.8Hz,3H),1.23-1.30(m,1 H),1.38(s,3H),1.49-1.55(m,2H),1.68-1.75(m,1H),2.04-2.19(m,2H),3.75(dd,J=10.8,7.6Hz,1H).

[0279] Synthesis Example 126 Synthesis of (1S,2S,3R,4S)-1-isopropyl-2,4-dimethyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptane(1-74) In Synthesis Example 47, (1S,2R,4S)-4-isopropyl-1,3-dimethyl-7-oxabicyclo[2.2.1]heptan-2-ol was used instead of (1S,2R,3S,4S)-4-isopropyl-1,3-dimethyl-7-oxabicyclo[2.2.1]heptan-2-ol, and the same reaction and treatment were carried out to obtain the title compound (yield 88%) as a colorless liquid.

[0280] Synthesis Example 127 Synthesis of (1S,2R,3R,4S)-1-isopropyl-2,4-dimethyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptane(1-75) In Synthesis Example 47, (1S,2R,4S)-4-isopropyl-1,3-dimethyl-7-oxabicyclo[2.2.1]heptan-2-ol was used instead of (1S,2R,3R,4S)-4-isopropyl-1,3-dimethyl-7-oxabicyclo[2.2.1]heptan-2-ol, and the same reaction and treatment were carried out to obtain the title compound (yield 76%) as a colorless liquid.

[0281] Synthesis Example 128 Synthesis of (1S,2R,3S,4S)-2-[(2-fluorobenzyl)oxy]-4-isopropyl-1,3-dimethyl-7-oxabicyclo[2.2.1]heptane (1-83) In Synthesis Example 49, (1S,2R,4S)-4-isopropyl-1,3-dimethyl-7-oxabicyclo[2.2.1]heptan-2-ol was used instead of (1S,2R,3S,4S)-4-isopropyl-1,3-dimethyl-7-oxabicyclo[2.2.1]heptan-2-ol, and the same reaction and treatment were carried out to obtain the title compound (yield 80%) as a colorless liquid.

[0282] Synthesis Example 129 Synthesis of (1S,2R,3R,4S)-2-[(2-fluorobenzyl)oxy]-4-isopropyl-1,3-dimethyl-7-oxabicyclo[2.2.1]heptane (1-84) In Synthesis Example 49, (1S,2R,4S)-4-isopropyl-1,3-dimethyl-7-oxabicyclo[2.2.1]heptan-2-ol was used instead of (1S,2R,3R,4S)-4-isopropyl-1,3-dimethyl-7-oxabicyclo[2.2.1]heptan-2-ol, and the same reaction and treatment were carried out to obtain the title compound (yield 79%) as a colorless liquid.

[0283] Synthesis Example 130 Synthesis of (1S,2R,3R,4S)-2-[(2-chlorobenzyl)oxy]-4-isopropyl-1,3-dimethyl-7-oxabicyclo[2.2.1]heptane (1-90) In Synthesis Example 55, (1S,2R,4S)-4-isopropyl-1,3-dimethyl-7-oxabicyclo[2.2.1]heptan-2-ol was used instead of (1S,2R,3R,4S)-4-isopropyl-1,3-dimethyl-7-oxabicyclo[2.2.1]heptan-2-ol, and the same reaction and treatment were carried out to obtain the title compound (yield 72%) as a colorless liquid.

[0284] Synthesis Example 131 Synthesis of (1S,2R,3S,4S)-2-[(2,6-difluorobenzyl)oxy]-4-isopropyl-1,3-dimethyl-7-oxabicyclo[2.2.1]heptane (1-102) The same reaction and treatment were carried out using (1S,2R,3S,4S)-4-isopropyl-1,3-dimethyl-7-oxabicyclo[2.2.1]heptan-2-ol instead of (1S,2R,4S)-4-isopropyl-1,3-dimethyl-7-oxabicyclo[2.2.1]heptan-2-ol in Synthesis Example 53, to obtain the title compound (yield 83%) as a colorless liquid.

[0285] Synthesis Example 132 Synthesis of (1S,2R,3R,4S)-2-[(2,6-difluorobenzyl)oxy]-4-isopropyl-1,3-dimethyl-7-oxabicyclo[2.2.1]heptane(1-103) The same reaction and treatment were carried out using (1S,2R,3R,4S)-4-isopropyl-1,3-dimethyl-7-oxabicyclo[2.2.1]heptan-2-ol instead of (1S,2R,4S)-4-isopropyl-1,3-dimethyl-7-oxabicyclo[2.2.1]heptan-2-ol in Synthesis Example 53, to obtain the title compound (yield 81%) as a colorless liquid.

[0286] Synthesis Example 133 Synthesis of (1S,2R,3R,4S)-1-isopropyl-4-methyl-3-(pyridin-3-ylmethoxy)-7-oxabicyclo[2.2.1]heptan-2-ol(1-53) In Synthesis Example 3, 3-[[[(1S,2R,3R,4S)-3-(1-ethoxyethoxy)-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]heptan-2-yl]oxy]methyl]pyridine was used in place of (1S,2R,3R,4S)-2-[(2-chlorobenzyl)oxy]-3-(1-ethoxyethoxy)-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]heptane, and the same reaction and treatment were carried out as above to obtain the title compound (yield 39%) as a colorless liquid.

[0287] Synthesis Example 134 Synthesis of (1S,2R,3R,4S)-1-isopropyl-4-methyl-3-(pyridin-4-ylmethoxy)-7-oxabicyclo[2.2.1]heptan-2-ol(1-55) In Synthesis Example 3, using 4-[[[(1S,2R,3R,4S)-3-(1-ethoxyethoxy)-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]heptane instead of (1S,2R,3R,4S)-2-[(2-chlorobenzyl)oxy]-3-(1-ethoxyethoxy)-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]heptan-2-yl]oxy]methyl]pyridine, the same reaction and treatment were carried out to obtain the title compound (yield 39%) as a colorless liquid.

[0288] Synthesis Example 135 Synthesis of (1S,2R,3R,4S)-1-isopropyl-4-methyl-3-(thiophen-2-ylmethoxy)-7-oxabicyclo[2.2.1]heptan-2-ol(1-57) In Synthesis Example 3, (1S,2R,3R,4S)-2-[(2-chlorobenzyl)oxy]-3-(1-ethoxyethoxy)-4-isopropyl-1-methyl-7-oxabicyclo[2.2.1]heptane was replaced with (1S,2R,3R,4S)-2-(1-ethoxyethoxy)-1-isopropyl-4-methyl-3-(thiophen-2-ylmethoxy)-7-oxabicyclo[2.2.1]heptane, and the same reaction and treatment were carried out to obtain the title compound (yield 65%) as a colorless liquid.

[0289] Synthesis Example 136 Synthesis of (1S,3S,4S)-1-isopropyl-4-methyl-3-(pyridin-3-ylmethoxy)-7-oxabicyclo[2.2.1]heptan-2-one(2-32) In Synthesis Example 84, (1S,2R,3R,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-ol was replaced with (1S,2R,3R,4S)-1-isopropyl-4-methyl-3-(pyridin-3-ylmethoxy)-7-oxabicyclo[2.2.1]heptan-2-ol, and the same reaction and treatment were carried out to obtain the title compound (yield 50%) as a colorless liquid.

[0290] Synthesis Example 137 Synthesis of (1S,3S,4S)-1-isopropyl-4-methyl-3-(pyridin-4-ylmethoxy)-7-oxabicyclo[2.2.1]heptan-2-one(2-34) In Synthesis Example 84, (1S,2R,3R,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-ol was replaced with (1S,2R,3R,4S)-1-isopropyl-4-methyl-3-(pyridin-4-ylmethoxy)-7-oxabicyclo[2.2.1]heptan-2-ol, and the same reaction and treatment were carried out to obtain the title compound (yield 37%) as a colorless liquid.

[0291] Synthesis Example 138 Synthesis of (1S,3S,4S)-1-isopropyl-4-methyl-3-(thiophen-2-ylmethoxy)-7-oxabicyclo[2.2.1]heptan-2-one(2-36) In Synthesis Example 84, (1S,2R,3R,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-ol was replaced with (1S,2R,3R,4S)-1-isopropyl-4-methyl-3-(thiophen-2-ylmethoxy)-7-oxabicyclo[2.2.1]heptan-2-ol, and the same reaction and treatment were carried out to obtain the title compound (yield 83%) as a colorless liquid.

[0292] Synthesis Example 139 Synthesis of (1S,3R,4S,E)-1-isopropyl-4-methyl-3-(pyridin-3-ylmethoxy)-7-oxabicyclo[2.2.1]heptan-2-one oxime(2-219) In Synthesis Example 98, (1S,3S,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-one was used instead of (1S,3S,4S)-1-isopropyl-4-methyl-3-(pyridin-3-ylmethoxy)-7-oxabicyclo[2.2.1]heptan-2-one, and the same reaction and treatment were carried out to obtain the title compound as a colorless liquid (yield 100%).

[0293] Synthesis Example 140 Synthesis of (1S,3R,4S,E)-1-isopropyl-4-methyl-3-(pyridin-4-ylmethoxy)-7-oxabicyclo[2.2.1]heptan-2-one oxime(2-221) In Synthesis Example 98, (1S,3S,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-one was used instead of (1S,3S,4S)-1-isopropyl-4-methyl-3-(pyridin-4-ylmethoxy)-7-oxabicyclo[2.2.1]heptan-2-one, and the same reaction and treatment were carried out to obtain the title compound as a colorless liquid (yield 100%).

[0294] Synthesis Example 141 Synthesis of (1S,3R,4S,E)-1-isopropyl-4-methyl-3-(thiophen-2-ylmethoxy)-7-oxabicyclo[2.2.1]heptan-2-one oxime(2-223) In Synthesis Example 98, (1S,3S,4S)-1-isopropyl-4-methyl-3-[(2-methylbenzyl)oxy]-7-oxabicyclo[2.2.1]heptan-2-one was used instead of (1S,3S,4S)-1-isopropyl-4-methyl-3-(thiophen-2-ylmethoxy)-7-oxabicyclo[2.2.1]heptan-2-one, and the same reaction and treatment were carried out to obtain the title compound (yield 93%) as a colorless liquid.

[0295] The compounds according to the present invention produced according to the above synthesis examples and production methods 1 The 1 HNMR spectrum (CDCl 3 ) σ (ppm) value, melting point (° C.), etc. are shown in Tables 3 and 4. 1 HNMR data was measured using a JNM-ECS400 spectrometer (manufactured by JEOL Ltd.) or the like.

[0296] [Table 19]

[0297] [Table 20]

[0298] [Table 21]

[0299] [Table 22]

[0300] [Table 23]

[0301] [Table 24]

[0302] [Table 25]

[0303] [Table 26]

[0304] [Table 27]

[0305] [Table 28]

[0306] [Table 29]

[0307] The following Reference Examples show synthesis examples in which starting materials for the above synthesis are synthesized from commercially available products, but the present invention is not limited to these examples.

[0308] Reference example 1 Synthesis of (1S,2R)-4-isopropyl-1-methylcyclohex-3-ene-1,2-diol Methanesulfonamide (2.69 g, 28.3 mmol) was added to a solution of AD-mix-β (Sigma Aldrich) (40.0 g) in tert-butanol (100 mL) and water (100 mL) and stirred at room temperature for 30 minutes. α-Terpinene (5.10 mL, 28.3 mmol) was added to this mixture at 0°C and stirred at 0°C for 17 hours. Sodium sulfite (15.0 g) was added to the reaction mixture and the temperature was raised to room temperature. The reaction mixture was extracted with ethyl acetate, and the extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane) to obtain the title compound as a colorless liquid (yield 3.24 g, 67%). 1 HNMR spectrum (CDCl3) δ1.02(d,J=6.8Hz,3H),1.03(d,J=6.8Hz,3H),1.21(s,3H),1.56-1.64(m,1H),1.80(ddd,J=1 3.2,7.5,5.9,1H),1.95-2.04(m,2H),2.12-2.27(m,2H),2.29(s,1H),3.80(d,J=5.2Hz,1H),5.43-5.45(m,1H).

[0309] Reference example 2 Synthesis of (1S,2R)-2-((tert-butyldimethylsilyl)oxy)-4-isopropyl-1-methylcyclohex-3-en-1-ol (1S,2R)-4-isopropyl-1-methylcyclohex-3-ene-1,2-diol(514 Imidazole (513 mg, 7.54 mmol) and tert-butylchlorodimethylsilane (909 mg, 6.03 mmol) were added to a solution of 1 mg (3.02 mmol) of methylisothiazolinone in dimethylformamide (30 mL), and the mixture was stirred at room temperature for 24 hours. Saturated aqueous sodium bicarbonate solution was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (extractant: ethyl acetate / n-hexane) to obtain the title compound as a colorless liquid (yield 836 mg, 97%). 1 HNMR spectrum (CDCl3) δ0.12(s,6H),0.92(s,9H),1.00(d,J=6.8Hz,3H),1.01(d,J=6.8Hz,3H),1.14(s,3H),1.4 8-1.56(m,1H),1.81-1.94(m,2H),2.12-2.23(m,2H),2.78(s,1H),3.87(d,J=3.2Hz,1H),5.24-5.25(m,1H).

[0310] Reference example 3 (1R,2R,3S,6R)-2-((tert-butyldimethylsilyl)oxy)-6-isopropyl-3-methyl-7-oxabicyclo[4.1.0]heptan-3-ol and Synthesis of (1S,2R,3S,6S)-2-((tert-butyldimethylsilyl)oxy)-6-isopropyl-3-methyl-7-oxabicyclo[4.1.0]heptan-3-ol 3-Chloroperbenzoic acid (303 mg, 1.76 mmol) was added to a dichloromethane solution (15 mL) of (1S,2R)-2-((tert-butyldimethylsilyl)oxy)-4-isopropyl-1-methylcyclohex-3-en-1-ol (417 mg, 1.46 mmol), and the mixture was stirred at room temperature for 1.5 hours. A saturated aqueous solution of sodium bicarbonate was poured into the reaction mixture, which was then extracted with dichloromethane. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane) to give a colorless liquid (1R,2R,3S,6R)-2-((tert-butyldimethylsilyl)oxy)-6-isopropyl-3-methyl-7-oxabicyclo[4.1.0]heptan-3-ol (yield 212 mg, 48%) and a colorless liquid (1S,2R,3S,6S)-2-((tert-butyldimethylsilyl)oxy)-6-isopropyl-3-methyl-7-oxabicyclo[4.1.0]heptan-3-ol (yield 200 mg, 45%).

[0311] (1R,2R,3S,6R)-2-((tert-butyldimethylsilyl)oxy)-6-isopropyl-3-methyl-7-oxabicyclo[4.1.0]heptan-3-ol 1 HNMR spectrum (CDCl3) δ 0.13 (s, 3H), 0.18 (s, 3H), 0.955 (s, 9H), 0.957 (d, J = 6.8H, 3H), 0.98 (d, J = 6.8H, 3H), 1.09 (s, 3H), 1.22 - 1.34 (m, 1H), 1.47 - 1.56 (m, 2H), 1.64 - 1.72 (m, 1H), 2.04 (ddd, J = 14.6, 12.4, 5.4Hz, 1H), 2.57 (d, J = 2.4Hz, 1H), 2.63 (s, 1H), 3.54 (s, 1H).

[0312] (1S,2R,3S,6S)-2-((tert-butyldimethylsilyl)oxy)-6-isopropyl-3-methyl-7-oxabicyclo[4.1.0]heptan-3-ol 1 HNMR spectrum (CDCl3) δ 0.14 (s, 3H), 0.18 (s, 3H), 0.955 (d, J = 6.8H, 3H), 0.959 (s, 9H), 0.98 (d, J = 6.8H, 3H), 1.11 (s, 3H), 1.20 - 1.34 (m, 1H), 1.41 - 1.55 (m, 1H), 1.68 - 1.79 (m, 2H), 1.90 - 2.01 (m, 1H), 2.96 (d, J = 2.8Hz, 1H), 3.14 (s, 1H), 3.69 (d, J = 2.8H, 1H).

[0313] Reference Example 4 Synthesis of (1S,2R)-4-isopropyl-1-methyl-2-((2-methylbenzyl)oxy)cyclohex-3-en-1-ol Sodium hydride (55% dispersion in mineral oil, 374 mg, 8.56 mmol) was added to a solution of (1S,2R)-4-isopropyl-1-methylcyclohex-3-ene-1,2-diol (730 mg, 4.28 mmol) in dimethylformamide (43 mL) and stirred at 0°C for 1 hour. 2-Methylbenzyl bromide (0.82 mL, 6.43 mmol) was added to the reaction mixture and stirred at room temperature for 19 hours. Saturated aqueous ammonium chloride solution was poured into the reaction mixture, which was then extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane) to give the title compound (1.03 g, 82%) as a colorless liquid. 1 HNMR spectrum (CDCl3) δ1.01(d,J=6.8Hz,3H),1.02(d,J=6.8Hz,3H),1.17(s,3H),1.80-1.90(m,1H),1.91-2.02(m,1H),2.13-2.29(m,2H) ,2.35(s,3H),2.84(s,1H),3.58(d,J=4.0Hz,1H),4.55(d,J=11.2Hz,1H),4.75(d,J=11.6Hz,1H),5.51-5.57(m,1H),7.13-7.36(m,4H).

[0314] Reference example 5 (1R,2R,3S,6R)-6-isopropyl-3-methyl-2-((2-methylbenzyl)oxy)-7-oxabicyclo[4.1.0]heptan-3-ol and Synthesis of (1S,2R,3S,6S)-6-isopropyl-3-methyl-2-((2-methylbenzyl)oxy)-7-oxabicyclo[4.1.0]heptan-3-ol 3-Chloroperbenzoic acid (690 mg, 4.00 mmol) was added to a dichloromethane solution (33 mL) of (1S,2R)-4-isopropyl-1-methyl-2-((2-methylbenzyl)oxy)cyclohex-3-en-1-ol (908 mg, 3.30 mmol), and the mixture was stirred at room temperature for 39 hours. A saturated aqueous solution of sodium bicarbonate was poured into the reaction mixture, which was then extracted with dichloromethane. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (extractant: ethyl acetate / n-hexane) to give a colorless liquid (1R,2R,3S,6R)-6-isopropyl-3-methyl-2-((2-methylbenzyl)oxy)-7-oxabicyclo[4.1.0]heptan-3-ol (yield 526 mg, 55%) and a colorless liquid (1S,2R,3S,6S)-6-isopropyl-3-methyl-2-((2-methylbenzyl)oxy)-7-oxabicyclo[4.1.0]heptan-3-ol (yield 393 mg, 41%).

[0315] (1R,2R,3S,6R)-6-isopropyl-3-methyl-2-((2-methylbenzyl)oxy)-7-oxabicyclo[4.1.0]heptan-3-ol 1 HNMR spectrum (CDCl3) δ0.97(d,J=6.8Hz,3H),1.00(d,J=6.8Hz,3H),1.13(s,3H),1.24-1.37(m,1H),1.49-1.60(m,2H),1.65-1.75(m,1H),1.99 -2.12(m,1H),2.36(d,J=2.4Hz,1H),2.40(s,3H),2.89(s1H),3.31(s1H),4.62(d,J=10.8Hz,1H),4.89(d,J=11.6Hz,1H),7.18-7.39(m,4H).

[0316] (1S,2R,3S,6S)-6-isopropyl-3-methyl-2-((2-methylbenzyl)oxy)-7-oxabicyclo[4.1.0]heptan-3-ol 1 HNMR spectrum (CDCl3) δ0.95(d,J=6.8Hz,3H),0.99(d,J=6.8Hz,3H),1.17(s,3H),1.23-1.35(m,2H),1.49(m,1H),1.68-1.84(m,2H),1.91-2.03(m ,1H),2.42(s,3H),3.16(d,J=2.8Hz,1H),3.35(s1H),3.45(d,J=2.8Hz, 1H),4.69(d,J=12.0Hz,1H),4.89(d,J=11.6Hz,1H),7.14-7.43(m,4H).

[0317] Reference example 6 Synthesis of (1R,2S)-4-isopropyl-1-methylcyclohex-3-ene-1,2-diol Methanesulfonamide (680 mg, 7.15 mmol) was added to a solution of AD-mix-α (Sigma Aldrich) (10.0 g) in tert-butanol (40 mL) and water (40 mL) and stirred at room temperature for 30 minutes. α-Terpinene (1.16 mL, 7.14 mmol) was added to this mixture at 0°C and stirred at 0°C for 72 hours. Sodium sulfite (10.7 g) was added to the reaction mixture and the temperature was raised to room temperature. The reaction mixture was extracted with ethyl acetate, and the extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane) to obtain the title compound as a colorless liquid (yield: 914 mg, 75%). 1 HNMR spectrum (CDCl3) δ1.02(d,J=6.8Hz,3H),1.03(d,J=6.8Hz,3H),1.21(s,3H),1.56-1.64(m,1H),1.80(ddd,J=1 3.2,7.5,5.9,1H),1.95-2.04(m,2H),2.12-2.27(m,2H),2.29(s,1H),3.80(d,J=5.2Hz,1H),5.43-5.45(m,1H).

[0318] Reference example 7 Synthesis of (1R,2S)-2-((tert-butyldimethylsilyl)oxy)-4-isopropyl-1-methylcyclohex-3-en-1-ol (1R,2S)-4-isopropyl-1-methylcyclohex-3-ene-1,2-diol(832 Imidazole (678 mg, 9.96 mmol) and tert-butylchlorodimethylsilane (1.47 g, 9.75 mmol) were added to a solution of 1.2 mg (4.89 mmol) of 1.2 mg of methylisothiazolinone in dimethylformamide (40 mL), and the mixture was stirred at room temperature for 21 hours. Saturated aqueous sodium bicarbonate solution was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (extractant: ethyl acetate / n-hexane) to obtain the title compound as a colorless liquid (yield 1.16 g, 84%). 1 HNMR spectrum (CDCl3) δ0.12(s,6H),0.92(s,9H),1.00(d,J=6.8Hz,3H),1.01(d,J=6.8Hz,3H),1.14(s,3H),1.4 8-1.56(m,1H),1.81-1.94(m,2H),2.12-2.23(m,2H),2.78(s,1H),3.87(d,J=3.2Hz,1H),5.24-5.25(m,1H).

[0319] Reference example 8 (1S,2S,3R,6S)-2-((tert-butyldimethylsilyl)oxy)-6-isopropyl-3-methyl-7-oxabicyclo[4.1.0]heptan-3-ol and Synthesis of (1R,2S,3R,6R)-2-((tert-butyldimethylsilyl)oxy)-6-isopropyl-3-methyl-7-oxabicyclo[4.1.0]heptan-3-ol 3-Chloroperbenzoic acid (1.31 g, 5.31 mmol) was added to a dichloromethane solution (40 mL) of (1R,2S)-2-((tert-butyldimethylsilyl)oxy)-4-isopropyl-1-methylcyclohex-3-en-1-ol (1.16 g, 4.08 mmol), and the mixture was stirred at room temperature for 12 hours. A saturated aqueous solution of sodium bicarbonate was poured into the reaction mixture, which was then extracted with dichloromethane. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane) to give a colorless liquid (1S,2S,3R,6S)-2-((tert-butyldimethylsilyl)oxy)-6-isopropyl-3-methyl-7-oxabicyclo[4.1.0]heptan-3-o (yield 642 mg, 52%) and a colorless liquid (1R,2S,3R,6R)-2-((tert-butyldimethylsilyl)oxy)-6-isopropyl-3-methyl-7-oxabicyclo[4.1.0]heptan-3-ol (yield 519 mg, 42%).

[0320] (1S,2S,3R,6S)-2-((tert-butyldimethylsilyl)oxy)-6-isopropyl-3-methyl-7-oxabicyclo[4.1.0]heptan-3-ol 1 HNMR spectrum (CDCl3) δ0.13(s,3H),0.18(s,3H),0.955(s,9H),0.957(d,J=6.8H,3H),0.98(d,J=6.8H,3H),1.09(s,3H),1.22-1.34( m,1H),1.47-1.56(m,2H),1.64-1.72(m,1H),2.04(ddd,J=14.6,12.4,5.4Hz,1H),2.57(d,J=2.4Hz,1H),2.63(s,1H),3.54(s,1H).

[0321] (1R,2S,3R,6R)-2-((tert-butyldimethylsilyl)oxy)-6-isopropyl-3-methyl-7-oxabicyclo[4.1.0]heptan-3-ol 1 HNMR spectrum (CDCl3) δ0.14(s,3H),0.18(s,3H),0.955(d,J=6.8H,3H),0.959(s,9H),0.98(d,J=6.8H,3H),1.11(s,3H),1.20-1 .34(m,1H),1.41-1.55(m,1H),1.68-1.79(m,2H),1.90-2.01(m,1H),2.96(d,J=2.8Hz,1H),3.14(s,1H),3.69(d,J=2.8H,1H).

[0322] Reference example 9 Synthesis of (1R,2S)-4-isopropyl-1-methyl-2-((2-methylbenzyl)oxy)cyclohex-3-en-1-ol Sodium hydride (55% dispersion in mineral oil, 191 mg, 4.72 mmol) was added to a solution of (1R,2S)-4-isopropyl-1-methylcyclohex-3-ene-1,2-diol (321 mg, 1.88 mmol) in dimethylformamide (10 mL) and stirred at 0°C for 30 minutes. 2-Methylbenzyl bromide (0.51 mL, 3.78 mmol) was added to the reaction mixture and stirred at room temperature for 14 hours. Saturated aqueous ammonium chloride solution was poured into the reaction mixture, which was then extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane) to give the title compound (387 mg, 75%) as a colorless liquid. 1HNMR spectrum (CDCl3) δ1.01(d,J=6.8Hz,3H),1.02(d,J=6.8Hz,3H),1.17(s,3H),1.80-1.90(m,1H),1.91-2.02(m,1H),2.13-2.29(m,2H) ,2.35(s,3H),2.84(s,1H),3.58(d,J=4.0Hz,1H),4.55(d,J=11.2Hz,1H),4.75(d,J=11.6Hz,1H),5.51-5.57(m,1H),7.13-7.36(m,4H).

[0323] Reference example 10 (1S,2S,3R,6S)-6-isopropyl-3-methyl-2-((2-methylbenzyl)oxy)-7-oxabicyclo[4.1.0]heptan-3-ol and Synthesis of (1R,2S,3R,6R)-6-isopropyl-3-methyl-2-((2-methylbenzyl)oxy)-7-oxabicyclo[4.1.0]heptan-3-ol 3-Chloroperbenzoic acid (325 mg, 1.64 mmol) was added to a dichloromethane solution (8 mL) of (1R,2S)-4-isopropyl-1-methyl-2-((2-methylbenzyl)oxy)cyclohex-3-en-1-ol (267 mg, 1.26 mmol), and the mixture was stirred at room temperature for 12 hours and 30 minutes. A saturated aqueous solution of sodium bicarbonate was poured into the reaction mixture, which was then extracted with dichloromethane. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane) to give a colorless liquid (1S,2S,3R,6S)-6-isopropyl-3-methyl-2-((2-methylbenzyl)oxy)-7-oxabicyclo[4.1.0]heptan-3-ol (yield 133 mg, 44%) and a colorless liquid (1R,2S,3R,6R)-6-isopropyl-3-methyl-2-((2-methylbenzyl)oxy)-7-oxabicyclo[4.1.0]heptan-3-ol (yield 132 mg, 43%).

[0324] (1S,2S,3R,6S)-6-isopropyl-3-methyl-2-((2-methylbenzyl)oxy)-7-oxabicyclo[4.1.0]heptan-3-ol 1 HNMR スペクトル(CDCl3)δ0.97(d,J=6.8Hz,3H),1.00(d,J=6.8Hz,3H),1.13 (s,3H),1.24-1.37(m,1H),1.49-1.60(m,2H),1.65-1.75(m,1H),1.99 -2.12(m,1H),2.36(d,J=2.4Hz,1H),2.40(s,3H),2.89(s1H),3.31(s1H),4.62(d,J=10.8Hz,1H),4.89(d,J=11.6Hz,1H),7.18-7.39(m,4H).

[0325] (1R,2S,3R,6R)-6-isopropyl-3-methyl-2-((2-methylbenzyl)oxy)-7-oxabicyclo[4.1.0]heptan-3-ol 1 HNMR スペクトル(CDCl3)δ0.95(d,J=6.8Hz,3H),0.99(d,J=6.8Hz,3H),1.17( s,3H),1.23-1.35(m,2H),1.49(m,1H),1.68-1.84(m,2H),1.91-2.03(m ,1H),2.42(s,3H),3.16(d,J=2.8Hz,1H),3.35(s1H),3.45(d,J=2.8Hz, 1H),4.69(d,J=12.0Hz,1H),4.89(d,J=11.6Hz,1H),7.14-7.43(m,4H).

[0326] Reference Example 11 Synthesis of (1S,2R)-2-(benzyloxy)-4-isopropyl-1-methylcyclohex-3-en-1-ol Sodium hydride (55% dispersion in mineral oil, 808 mg, 18.5 mmol) was added to a solution of (1R,2S)-4-isopropyl-1-methylcyclohex-3-ene-1,2-diol (1.64 g, 9.63 mmol) in dimethylformamide (100 mL) and stirred at 0°C for 30 minutes. 2-Methylbenzyl bromide (1.37 mL, 11.6 mmol) was added to the reaction mixture and stirred at room temperature for 16 hours. Saturated aqueous ammonium chloride solution was poured into the reaction mixture, which was then extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane) to give the title compound (1.67 g, 67%) as a colorless liquid. 1 HNMR spectrum (CDCl3) δ1.01(d,J=6.8Hz,3H),1.02(d,J=6.8Hz,3H),1.17(s,3H),1.51-1.60(m,1H),1.80-1.90(m,1H),1.91-2.02(m,1H),2. 14-2.29(m,2H),2.84(s,3H),3.59(d,J=4.4Hz,1H),4.60(d,J=12.0Hz,1H),4.75(d,J=12.0Hz,1H),5.51-5.57(m,1H),7.25-7.40(m,5H).

[0327] Reference example 12 Synthesis of (1R,2R,3S,6R)-2-(benzyloxy)-6-isopropyl-3-methyl-7-oxabicyclo[4.1.0]heptan-3-ol and (1S,2R,3S,6S)-2-(benzyloxy)-6-isopropyl-3-methyl-7-oxabicyclo[4.1.0]heptan-3-ol 3-Chloroperbenzoic acid (1.93 g, 7.70 mmol) was added to a dichloromethane solution (60 mL) of (1S,2R)-2-(benzyloxy)-4-isopropyl-1-methylcyclohex-3-en-1-ol (1.67 g, 6.42 mmol), and the mixture was stirred at room temperature for 5 hours. A saturated aqueous solution of sodium bicarbonate was poured into the reaction mixture, which was then extracted with dichloromethane. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane) to give a colorless liquid (1R,2R,3S,6R)-2-(benzyloxy)-6-isopropyl-3-methyl-7-oxabicyclo[4.1.0]heptan-3-ol (yield 881 mg, 50%) and a colorless liquid (1S,2R,3S,6S)-2-(benzyloxy)-6-isopropyl-3-methyl-7-oxabicyclo[4.1.0]heptan-3-ol (yield 858 mg, 46%).

[0328] (1R,2R,3S,6R)-2-(benzyloxy)-6-isopropyl-3-methyl-7-oxabicyclo[4.1.0]heptan-3-ol 1 HNMR spectrum (CDCl3) δ0.97(d,J=6.8Hz,3H),1.00(d,J=6.8Hz,3H),1.13(s,3H),1.24-1.40(m,1H),1.51-1.60(m,2H),1.64- 1.76(m,1H),2.01-2.13(m,1H),2.88(s1H),3.31(s1H),4.64(d,J=12.0Hz,1H),4.87(d,J=12.0Hz,1H),7.28-7.40(m,5H).

[0329] (1S,2R,3S,6S)-2-(benzyloxy)-6-isopropyl-3-methyl-7-oxabicyclo[4.1.0]heptan-3-ol 1HNMR spectrum (CDCl3) δ0.95(d,J=6.8Hz,3H),0.99(d,J=6.8Hz,3H),1.17(s,3H),1.22-1.36(m,1H),1.48(m,1H),1.68-1.83(m,2H), 1.91-2.03(m,1H),3.15(d,J=2.0Hz,1H),3.44(d,J=2.0Hz,1H),4.70(d,J=12.0Hz,1H),4.87(d,J=11.6Hz,1H),7.25-7.50(m,5H).

[0330] Next, methods for formulating the compound of the present invention as a herbicide will be specifically explained using the following formulation examples. However, the herbicide is not limited to these formulation examples, and the herbicide can also be formulated by mixing it with various other additives in any ratio. Unless otherwise specified, "parts" means parts by mass, and "%" means % by mass.

[0331] Formulation example 1 (granules) 1 part of the compound of Synthesis Example 1, 1 part of calcium lignosulfonate, 1 part of lauryl sulfate, 30 parts of bentonite, and 67 parts of talc were mixed with 15 parts of water and kneaded in a kneader, followed by granulation in an extrusion granulator. Granules containing 1% of the herbicidal active ingredient can be obtained by drying in a fluidized bed dryer. Furthermore, granules can be obtained in the same manner as above, except that the compounds listed in Tables 1 and 2 are used instead of the compound of Synthesis Example 1.

[0332] Formulation Example 2 (flowable formulation) A flowable formulation containing 20% ​​of a herbicidal active ingredient can be obtained by uniformly mixing and grinding 20.0 parts of the compound of Synthesis Example 1, 2.0 parts of di-2-ethylhexyl sulfosuccinate sodium salt, 2.0 parts of polyoxyethylene nonylphenyl ether, 5.0 parts of propylene glycol, 0.5 parts of an antifoaming agent, and 70.5 parts of water in a wet ball mill. Furthermore, flowable formulations can be obtained in the same manner as above, except that the compounds listed in Tables 1 and 2 are used instead of the compound of Synthesis Example 1.

[0333] Formulation Example 3 (Dry flowable formulation) A dry flowable (water dispersible granule) containing 75% of the herbicidal active ingredient can be obtained by uniformly mixing and finely pulverizing 75 parts of the compound of Synthesis Example 1, 10 parts of naphthalenesulfonic acid formaldehyde condensate, 5 parts of sodium lauryl sulfate, 5 parts of white carbon, and 5 parts of clay. Furthermore, dry flowable (water dispersible granule) formulations can be obtained in the same manner as above, except that the compounds listed in Tables 1 and 2 are used instead of the compound of Synthesis Example 1.

[0334] Formulation Example 4 (wettable powder) A wettable powder containing 15% of a herbicidal active ingredient can be obtained by uniformly mixing 15 parts of the compound of Synthesis Example 1, 15 parts of white carbon, 3 parts of calcium lignosulfonate, 2 parts of polyoxyethylene alkyl ether, 5 parts of diatomaceous earth, and 60 parts of clay in a grinding mixer.Furthermore, wettable powders can be obtained in the same manner as above, except that the compounds listed in Tables 1 and 2 are used instead of the compound of Synthesis Example 1.

[0335] Formulation Example 5 (emulsion) An emulsifiable concentrate containing 20% ​​of the herbicidal active ingredient can be obtained by mixing 20 parts of the compound of Synthesis Example 1, 18 parts of polyoxyethylene styrylphenyl ether, 2 parts of calcium dodecylbenzenesulfonate, and 60 parts of xylene. Furthermore, emulsifiable concentrates can be obtained in the same manner as above, except that the compounds shown in Tables 1 and 2 are used instead of the compound of Synthesis Example 1.

[0336] Formulation Example 6 (powder) A dust containing 0.5% of the herbicidal active ingredient can be obtained by uniformly mixing and grinding 0.5 parts of the compound of Synthesis Example 1, 0.5 parts of white carbon, 0.5 parts of calcium stearate, 50.0 parts of clay, and 48.5 parts of talc. Furthermore, dusts can be obtained in the same manner as above, except that the compounds listed in Tables 1 and 2 are used instead of the compound of Synthesis Example 1.

[0337] Formulation Example 7 (Jumbo Formulation) 15 parts of the compound of Synthesis Example 1, 2 parts of sodium lauryl sulfate, 5 parts of di-2-ethylhexyl sulfosuccinate sodium salt, 5 parts of carboxymethylcellulose sodium salt, 35 parts of Shirasu balloon, 10 parts of lactose, and 28 parts of expanded perlite were mixed, and then 35 parts of water was added and the mixture was kneaded in a kneader and then granulated in an extrusion granulator. This was dried in a fluidized bed dryer to obtain a jumbo formulation containing 15% of the herbicidal active ingredient. Furthermore, jumbo formulations can be obtained by the same method, except that the compounds listed in Tables 1 and 2 are used instead of the compound of Synthesis Example 1.

[0338] Next, test examples will be shown to illustrate the herbicidal effects of the 1,4-cineole derivatives of the present invention.

[0339] Test Example 1 Herbicidal effect test using rice soil treatment Paddy field soil was filled into a Wagner pot measuring 1 / 10,000 are, water was added, and a compound fertilizer (N:P:K = 16:16:16) was mixed in. The pot was then puddled. Thirty seeds each of barnyardgrass, broadleaf weeds (Lamium sieboldii and Monochoria vaginalis), and Scirpus juncoides were sown at a depth of 0-1 cm. The soil was flooded immediately after sowing, and the water depth was maintained at approximately 3 cm. Subsequent management was carried out in a glass greenhouse. Immediately after sowing, an emulsion prepared according to Formulation Example 5 using the compounds listed below was diluted with water, and the specified amount of the diluted solution was applied dropwise. The application rate of the active ingredient was equivalent to 120 g per 10 ares. This test was carried out in duplicate for each chemical concentration group, and 14 days after chemical treatment, the weed control rate (%) was calculated using the following formula (Equation 1).

[0340]

number

[0341] Representative examples include the above-mentioned compound numbers 1-22, 1-24, 1-25, 1-26, 1-28, 1-30, 1-32, 1-35, 1-37, 1-39, 1-41, 1-43, 1-45, 1-47, 1-50, 1-52, 1-55, 1-57, 1-61, 1-62, 1-73, 1-74, 1-75, 1-80, 1-82, 1-83, 1-84, 1-88, 1-90, 1-95, 1-97, 1-99, 1-101, 1-102, and 1-103. 3, 1-107, 1-141, 1-144, 1-146, 1-148, 1-171, 1-173, 1-175, 1-177, 1-179, 1-181, 1-183, 1-185, 1-187, 1-189, 1-192, 1-217, 1-225, 1-239, 1-247, 1-250, 1-252, 1-254, 1-256, 1-258, 1-261, 1-263, 1-266, 1-273, 1-275, 1-283, 1- 291, 2-1, 2-3, 2-5, 2-7, 2-9, 2-11, 2-14, 2-16, 2-18, 2-20, 2-22, 2-24, 2-26, 2-29, 2-32, 2-34, 2-36, 2-72, 2-74, 2-76, 2-78, 2-80, 2-82, 2-84, 2-86, 2-88, 2-90, 2-92, 2-94, 2-98, 2-100, 2-102, 2-104, 2-106, 2-110, 2-112, 2-116 The following compounds showed weed control rates of 80% or more against barnyardgrass: 2-118, 2-120, 2-122, 2-124, 2-126, 2-128, 2-191, 2-193, 2-195, 2-197, 2-199, 2-201, 2-203, 2-205, 2-207, 2-209, 2-211, 2-213, 2-216, 2-219, 2-221, 2-223, 2-227, 2-240, 2-247, 2-254, and 2-261. As representative examples, the compounds of compound numbers 1-24, 1-25, 1-30, 1-35, 1-37, 1-41, 1-45, 1-61, 1-74, 1-75, 1-83, 1-97, 1-101, 1-102, 1-103, 1-247, 2-11, 2-20, 2-26, 2-76, 2-78, 2-82, 2-88, 2-90, 2-94, 2-112, 2-191, 2-197, 2-199, 2-201, 2-203, 2-207, 2-213, 2-227, and 2-240 showed a weed control rate of 80% or more against Lindernia procumbens. Representative examples include the above-mentioned compound numbers 1-22, 1-24, 1-25, 1-30, 1-32, 1-35, 1-37, 1-41, 1-45, 1-61, 1-74, 1-75, 1-82, 1-83, 1-84, 1-90, 1-95, 1-97, 1-101, 1-102, 1-103, 1-247, 1-291, 2-1, 2-3, 2-11, 2-2 The compounds 0, 2-26, 2-72, 2-76, 2-78, 2-82, 2-88, 2-90, 2-94, 2-104, 2-112, 2-122, 2-191, 2-197, 2-199, 2-201, 2-203, 2-205, 2-207, 2-213, 2-227, 2-240, and 2-247 showed weed control rates of 80% or more against Monochoria vaginalis. Representative examples include the above-mentioned compound numbers 1-24, 1-25, 1-28, 1-30, 1-32, 1-35, 1-37, 1-41, 1-47, 1-50, 1-61, 1-62, 1-73, 1-74, 1-75, 1-80, 1-82, 1-83, 1-84, 1-88, 1-90, 1-97, 1-101, 1-102, 1-103, 1-141, 1-144, 1-146, 1-173, 1-175, 1-177, 1-185, 1-189, 1-247, 1-248, 1-250, 1-251, 1-252, 1-253, 1-254, 1-255, 1-256, 1-257, 1-258, 1-259, 1-260, 1-261, 1-262, 1-263, 1-264, 1-265, 1-266, 1-267, 1-268, 1-269, 1-270, 1-271, 1-272, 1-273, 1-274, 1-275, 1-276, 1-277, 1-278, 1-279, 1-280, 1-281, 1-282, 1-283, 1-284, 1-288, 1-290, 1-300, 1-301, 1-302 Compounds 52, 1-254, 1-256, 1-291, 2-3, 2-5, 2-7, 2-9, 2-11, 2-20, 2-26, 2-72, 2-76, 2-78, 2-82, 2-90, 2-94, 2-104, 2-112, 2-191, 2-193, 2-195, 2-197, 2-199, 2-201, 2-203, 2-205, 2-207, 2-213, 2-227, 2-240, and 2-247 showed weed control rates of 80% or more against Scirpus juncoides.

[0342] Test Example 2 Herbicidal effect test using rice growing season treatment Paddy field soil was filled into Wagner pots measuring 1 / 10,000 ares in area, water was added, and a chemical fertilizer (N:P:K = 16:16:16) was mixed in. The pots were then puddled. Thirty seeds each of barnyardgrass, broadleaf weeds (Lamium sieboldii and Monochoria vaginalis), and Scirpus juncoides were sown at a depth of 0-1 cm. Immediately after sowing, the pots were flooded with water, maintaining the water depth at approximately 3 cm. Subsequent management was carried out in a glasshouse. Seven days after sowing, an emulsion prepared according to Formulation Example 5 using the compounds listed below was diluted with water, and the specified amount of the diluted solution was applied dropwise. The application rate of the active ingredient was equivalent to 120 g per 10 ares. The test was conducted in duplicate for each concentration plot. 14 days after treatment, the weed control rate (%) was calculated using the following formula (Equation 1).

[0343] Representative examples include the above-mentioned compound numbers 1-22, 1-24, 1-25, 1-26, 1-28, 1-30, 1-32, 1-35, 1-37, 1-39, 1-41, 1-43, 1-45, 1-47, 1-50, 1-53, 1-55, 1-57, 1-61, 1-62, 1-73, 1-74, 1-75, 1-80, 1-82, 1-83, 1-84, 1-88, 1-90, 1-95, 1-97, 1-99, 1-101, 1-102, and 1-103. 3, 1-107, 1-141, 1-144, 1-146, 1-148, 1-171, 1-173, 1-175, 1-177, 1-179, 1-181, 1-183, 1-185, 1-187, 1-189, 1-192, 1-217, 1-225, 1-239, 1-247, 1-250, 1-252, 1-254, 1-256, 1-258, 1-261, 1-263, 1-266, 1-273, 1-275, 1-283, 1- 291, 2-1, 2-3, 2-5, 2-7, 2-9, 2-11, 2-14, 2-16, 2-18, 2-20, 2-22, 2-24, 2-26, 2-29, 2-32, 2-34, 2-36, 2-72, 2-74, 2-76, 2-78, 2-80, 2-82, 2-84, 2-86, 2-88, 2-90, 2-92, 2-94, 2-98, 2-100, 2-102, 2-104, 2-106, 2-110, 2-112, 2-116 The following compounds showed weed control rates of 80% or more against barnyardgrass: 2-118, 2-120, 2-122, 2-124, 2-126, 2-128, 2-191, 2-193, 2-195, 2-197, 2-199, 2-201, 2-203, 2-205, 2-207, 2-209, 2-211, 2-213, 2-216, 2-219, 2-221, 2-223, 2-227, 2-240, 2-247, 2-254, and 2-261.

[0344] As representative examples, the compounds Nos. 1-24, 1-25, 1-28, 1-30, 1-41, 1-61, 1-74, 1-75, 1-82, 1-83, 1-84, 1-88, 1-90, 1-101, 1-102, 1-247, 2-11, 2-20, 2-26, 2-82, 2-88, 2-90, 2-94, 2-112, 2-191, 2-197, 2-203, 2-205, 2-207, 2-213, 2-227, and 2-240 showed weed control rates of 80% or more against Lindernia procumbens.

[0345] Representative examples include the above-mentioned compound numbers 1-22, 1-24, 1-25, 1-30, 1-32, 1-41, 1-61, 1-62, 1-74, 1-75, 1-83, 1-84, 1-90, 1-97, 1-101, 1-102, 1-103, 1-225, 1-247, 2-1, 2-11, 2-14, and 2-16. The following compounds showed weed control rates of 80% or more against Monochoria vaginalis.

[0346] Representative examples include the above-mentioned compound numbers 1-24, 1-25, 1-28, 1-30, 1-32, 1-41, 1-47, 1-50, 1-61, 1-62, 1-73, 1-74, 1-75, 1-80, 1-82, 1-83, 1-84, 1-88, 1-90, 1-95, 1-97, 1-101, 1-102, 1-103, 1-141, 1-144, 1-146, 1-148, 1-173, 1-175, 1-177, 1-185, 1-189, 1-200, 1-201, 1-202, 1-203, 1-204, 1-205, 1-206, 1-207, 1-208, 1-210, 1-211, 1-212, 1-213, 1-214, 1-215, 1-216, 1-217, 1-218, 1-219, 1-220, 1-221, 1-222, 1-223, 1-224, 1-225, 1-226, 1-227, 1-228, 1-229, 1-230, 1-231, 1-232, 1-233, 1-234, 1-235, 1-236, 1-237, 1-238, 1-239, 1-240, 1-241, 1-24 Compounds 47, 1-252, 1-254, 1-256, 2-5, 2-7, 2-9, 2-11, 2-14, 2-16, 2-20, 2-26, 2-82, 2-88, 2-90, 2-94, 2-98, 2-100, 2-104, 2-112, 2-191, 2-193, 2-195, 2-197, 2-201, 2-203, 2-205, 2-207, 2-213, 2-227, and 2-240 showed weed control rates of 80% or more against Scirpus juncoides.

[0347] Test Example 3 Testing herbicidal efficacy by treating field soil 36cm 2 Pots of this size were filled with field soil (alluvial loam), and the top 1 cm of soil was uniformly mixed with 20 seeds each of Digitaria adscendens, Barnyardgrass, Chenopodium album, and Redroot pigweed, and the surface layer was lightly pressed down. One day after sowing, an emulsion prepared according to Formulation Example 5 using the compounds shown below was diluted with water, and the diluted solution was sprayed onto the soil surface at a rate of 100 liters per 10 ares. This was equivalent to an application rate of 120 g of active ingredient per 10 ares. 14 days after treatment, the herbicidal effect was evaluated using the same criteria as in Test Example 1.

[0348] Representative examples include the above-mentioned compound numbers 1-22, 1-24, 1-25, 1-26, 1-28, 1-30, 1-32, 1-35, 1-37, 1-39, 1-41, 1-43, 1-45, 1-47, 1-50, 1-53, 1-55, 1-57, 1-61, 1-62, 1-73, 1-74, 1-75, 1-80, 1-82, 1-83, 1-84, 1-88, 1-90, 1-95, 1-97, 1-99, 1-101, 1-102, 1-103, 1-104, 1-105, 1-106, 1-107, 1-108, 1-109, 1-210, 1-211, 1-212, 1-213, 1-214, 1-215, 1-216, 1-217, 1-218, 1-219, 1-220, 1-221, 1-222, 1-223, 1-224, 1-225, 1-226, 1-227, 1-228, 1-229, 1-230, 1-231, 1-232, 1-233, 1-234, 1-235, 1-236, 1-237, 1-238, 1-239, 1-240, 1-241, 1-242, 1-243, 1-244, 1 03, 1-107, 1-141, 1-144, 1-146, 1-148, 1-171, 1-173, 1-175, 1-177, 1-179, 1-181, 1-183, 1-185, 1-187, 1-189, 1-192, 1-217, 1-225, 1-239, 1-247, 1-250, 1-252, 1-254, 1-256, 1-258, 1-261, 1-263, 1-266, 1-273, 1-275, 1-283, 1 -291, 2-1, 2-3, 2-5, 2-7, 2-9, 2-11, 2-14, 2-16, 2-18, 2-20, 2-22, 2-24, 2-26, 2-29, 2-32, 2-34, 2-36, 2-72, 2-74, 2-76, 2-78, 2-80, 2-82, 2-84, 2-86, 2-88, 2-90, 2-92, 2-94, 2-98, 2-100, 2-102, 2-104, 2-106, 2-110, 2-112, 2-1 Compounds 16, 2-118, 2-120, 2-122, 2-124, 2-126, 2-128, 2-191, 2-193, 2-195, 2-197, 2-199, 2-201, 2-203, 2-205, 2-207, 2-209, 2-211, 2-213, 2-216, 2-219, 2-221, 2-223, 2-227, 2-240, 2-247, 2-254, and 2-261 showed a weed control rate of 80% or more against crabgrass.

[0349] Representative examples include the above-mentioned compound numbers 1-22, 1-24, 1-25, 1-26, 1-28, 1-30, 1-32, 1-35, 1-37, 1-39, 1-41, 1-43, 1-45, 1-47, 1-50, 1-53, 1-55, 1-57, 1-61, 1-62, 1-73, 1-74, 1-75, 1-80, 1-82, 1-83, 1-84, 1-88, 1-90, 1-95, 1-97, 1-99, 1-101, 1-102, 1-103, 1-104, 1-105, 1-106, 1-107, 1-108, 1-109, 1-210, 1-211, 1-212, 1-213, 1-214, 1-215, 1-216, 1-217, 1-218, 1-219, 1-220, 1-221, 1-222, 1-223, 1-224, 1-225, 1-226, 1-227, 1-228, 1-229, 1-230, 1-231, 1-232, 1-233, 1-234, 1-235, 1-236, 1-237, 1-238, 1-239, 1-240, 1-241, 1-242, 1-243, 1-244, 1 03, 1-107, 1-141, 1-144, 1-146, 1-148, 1-171, 1-173, 1-175, 1-177, 1-179, 1-181, 1-183, 1-185, 1-187, 1-189, 1-192, 1-217, 1-225, 1-239, 1-247, 1-250, 1-252, 1-254, 1-256, 1-258, 1-261, 1-263, 1-266, 1-273, 1-275, 1-283, 1 -291, 2-1, 2-3, 2-5, 2-7, 2-9, 2-11, 2-14, 2-16, 2-18, 2-20, 2-22, 2-24, 2-26, 2-29, 2-32, 2-34, 2-36, 2-72, 2-74, 2-76, 2-78, 2-80, 2-82, 2-84, 2-86, 2-88, 2-90, 2-92, 2-94, 2-98, 2-100, 2-102, 2-104, 2-106, 2-110, 2-112, 2-1 Compounds 16, 2-118, 2-120, 2-122, 2-124, 2-126, 2-128, 2-191, 2-193, 2-195, 2-197, 2-199, 2-201, 2-203, 2-205, 2-207, 2-209, 2-211, 2-213, 2-216, 2-219, 2-221, 2-223, 2-227, 2-240, 2-247, 2-254, and 2-261 showed weed control rates of 80% or more against barnyardgrass.

[0350] As representative examples, the compounds Nos. 1-62, 1-82, 1-291, 2-3, 2-11, 2-90, 2-191, 2-199 and 2-227 showed a weed control rate of 80% or more against Chenopodium album.

[0351] As representative examples, the compounds Nos. 1-62, 1-82, 1-146, 1-148, 1-291, 2-3, 2-5, 2-11, 2-72, 2-90, 2-94, 2-191, 2-199 and 2-227 showed a weed control rate of 80% or more against redroot pigweed.

[0352] Test Example 4 Herbicidal effect test by foliar application to field crops 36cm 2 Pots of this size were filled with field soil (alluvial loam), and the top 1 cm of soil was uniformly mixed with 20 seeds each of crabgrass, barnyard grass, lamb's quarter, and red spider lily, and the surface layer was lightly pressed down. Seven days after sowing, an emulsion prepared according to Formulation Example 5 using the compounds listed below was diluted with water, and the diluted solution was sprayed onto the soil surface at a rate of 100 liters per 10 ares. This was equivalent to an application rate of 120 g of active ingredient per 10 ares. 14 days after treatment, the herbicidal effect was evaluated using the same criteria as in Test Example 1.

[0353] Representative examples include the above-mentioned compound numbers 1-22, 1-24, 1-25, 1-26, 1-28, 1-30, 1-32, 1-35, 1-37, 1-39, 1-41, 1-43, 1-45, 1-47, 1-50, 1-53, 1-55, 1-57, 1-61, 1-62, 1-73, 1-74, 1-75, 1-80, 1-82, 1-83, 1-84, 1-88, 1-90, 1-95, 1-97, 1-99, 1-101, 1-102, 1-103, 1-104, 1-105, 1-106, 1-107, 1-108, 1-109, 1-210, 1-211, 1-212, 1-213, 1-214, 1-215, 1-216, 1-217, 1-218, 1-219, 1-220, 1-221, 1-222, 1-223, 1-224, 1-225, 1-226, 1-227, 1-228, 1-229, 1-230, 1-231, 1-232, 1-233, 1-234, 1-235, 1-236, 1-237, 1-238, 1-239, 1-240, 1-241, 1-242, 1-243, 1-244, 1 03, 1-107, 1-141, 1-144, 1-146, 1-148, 1-171, 1-173, 1-175, 1-177, 1-179, 1-181, 1-183, 1-185, 1-187, 1-189, 1-192, 1-217, 1-225, 1-239, 1-247, 1-250, 1-252, 1-254, 1-256, 1-258, 1-261, 1-263, 1-266, 1-273, 1-275, 1-283, 1 -291, 2-1, 2-3, 2-5, 2-7, 2-9, 2-11, 2-14, 2-16, 2-18, 2-20, 2-22, 2-24, 2-26, 2-29, 2-32, 2-34, 2-36, 2-72, 2-74, 2-76, 2-78, 2-80, 2-82, 2-84, 2-86, 2-88, 2-90, 2-92, 2-94, 2-98, 2-100, 2-102, 2-104, 2-106, 2-110, 2-112, 2-1 Compounds 16, 2-118, 2-120, 2-122, 2-124, 2-126, 2-128, 2-191, 2-193, 2-195, 2-197, 2-199, 2-201, 2-203, 2-205, 2-207, 2-209, 2-211, 2-213, 2-216, 2-219, 2-221, 2-223, 2-227, 2-240, 2-247, 2-254, and 2-261 showed a weed control rate of 80% or more against crabgrass.

[0354] Representative examples include the above-mentioned compound numbers 1-22, 1-24, 1-25, 1-26, 1-28, 1-30, 1-32, 1-35, 1-37, 1-39, 1-41, 1-43, 1-45, 1-47, 1-50, 1-53, 1-55, 1-57, 1-61, 1-62, 1-73, 1-74, 1-75, 1-80, 1-82, 1-83, 1-84, 1-88, 1-90, 1-95, 1-97, 1-99, 1-101, 1-102, 1-103, 1-104, 1-105, 1-106, 1-107, 1-108, 1-109, 1-210, 1-211, 1-212, 1-213, 1-214, 1-215, 1-216, 1-217, 1-218, 1-219, 1-220, 1-221, 1-222, 1-223, 1-224, 1-225, 1-226, 1-227, 1-228, 1-229, 1-230, 1-231, 1-232, 1-233, 1-234, 1-235, 1-236, 1-237, 1-238, 1-239, 1-240, 1-241, 1-242, 1-243, 1-244, 1 03, 1-107, 1-141, 1-144, 1-146, 1-148, 1-171, 1-173, 1-175, 1-177, 1-179, 1-181, 1-183, 1-185, 1-187, 1-189, 1-192, 1-217, 1-225, 1-239, 1-247, 1-250, 1-252, 1-254, 1-256, 1-258, 1-261, 1-263, 1-266, 1-273, 1-275, 1-283, 1 -291, 2-1, 2-3, 2-5, 2-7, 2-9, 2-11, 2-14, 2-16, 2-18, 2-20, 2-22, 2-24, 2-26, 2-29, 2-32, 2-34, 2-36, 2-72, 2-74, 2-76, 2-78, 2-80, 2-82, 2-84, 2-86, 2-88, 2-90, 2-92, 2-94, 2-98, 2-100, 2-102, 2-104, 2-106, 2-110, 2-112, 2-1 Compounds 16, 2-118, 2-120, 2-122, 2-124, 2-126, 2-128, 2-191, 2-193, 2-195, 2-197, 2-199, 2-201, 2-203, 2-205, 2-207, 2-209, 2-211, 2-213, 2-216, 2-219, 2-221, 2-223, 2-227, 2-240, 2-247, 2-254, and 2-261 showed weed control rates of 80% or more against barnyardgrass.

[0355] As representative examples, the compounds Nos. 1-101, 1-247, 2-7, 2-11, 2-195, and 2-199 showed a weed control rate of 80% or more against Chenopodium album. As representative examples, the compounds Nos. 2-3, 2-7 and 2-195 showed a weed control rate of 80% or more against redroot pigweed. [Industrial Applicability]

[0356] According to the present invention, it is possible to provide novel 1,4-cineole derivatives having excellent herbicidal activity, synthetic intermediates thereof, and herbicides containing the 1,4-cineole derivatives. The present invention also provides a method for using a herbicide and a method for preparing an agrochemical composition. Although the present invention has been described in detail and with reference to specific embodiments, it will be apparent to those skilled in the art that various changes and modifications can be made without departing from the spirit and scope of the invention.

Claims

1. A 1,4-cineole derivative represented by the following general formula (1), (1'), (2) or (2'): 【Chemical 1】 (In the general formulas (1), (1'), (2) and (2'), R １ are each independently a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkyl group (which may be mono- or poly-substituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), a C3-C6 cycloalkyl-C1-C6 alkyl group (which may be mono- or poly-substituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), a C1-C6 alkoxy-C1-C6 alkyl group, a phenyl group (which may be mono- or poly-substituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), a heterocyclic ring (which may be mono- or poly-substituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), a C7-C11 aralkyl group (which may be mono- or poly-substituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), a C7-C11 aralkyl group (which may be mono- or poly-substituted with halogen atoms, cyano groups, nitro groups, a heterocyclic C1-C6 alkyl group (which may be mono- or poly-substituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), a phenoxy C1-C6 alkyl group (which may be mono- or poly-substituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), a C7-C11 aralkyloxy C1-C6 alkyl group (which may be mono- or poly-substituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), or a benzoyl C1-C6 alkyl group (which may be mono- or poly-substituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups). R ２ and R ３ each independently represents a hydrogen atom, a halogen atom, a hydroxyl group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 alkoxy-C1-C6 alkoxy group, a C1-C6 alkylcarbonyloxy group, a C1-C6 alkoxycarbonyloxy group, a C1-C6 alkylthiocarbonyloxy group, a C1-C6 alkylthiothiocarbonyloxy group, a C1-C6 alkylsulfonyloxy group, or a C1-C6 haloalkylsulfonyloxy group, and at least one of them is a substituent other than a hydrogen atom. ２ and R ３ two adjacent substituents, taken together with the carbons to which they are attached, form a 3- to 6-membered carbocyclic ring or a 3- to 6-membered heterocyclic ring having 1 to 4 heteroatoms independently selected from oxygen, sulfur, and nitrogen atoms, wherein the ring formed may have one or more substituents. X is an oxygen atom, a sulfur atom, or CR ４ R ５ , or NR ６ Represents. R ４ and R ５ each independently represents a hydrogen atom or a C1-C6 alkyl group. R ６ represents a hydrogen atom, a hydroxyl group, a C1-C6 alkyl group, a C1-C6 alkoxy group, an amino group, a C1-C6 alkylamino group, an aminocarbonylamino group, or a phenylamino group (which may be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group).

2. R １ each independently represent a phenyl group (which may be mono- or poly-substituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), a C7-C11 aralkyl group (which may be mono- or poly-substituted with halogen atoms, cyano groups, nitro groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, or C1-C6 haloalkoxy groups), a heterocyclic C1-C6 alkyl group (which may be mono- or poly-substituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), a phenoxy C1-C6 alkyl group (which may be mono- or poly-substituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), or a benzoyl C1-C6 alkyl group (which may be mono- or poly-substituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups), R ２ and R ３ each independently represents a hydrogen atom, a halogen atom, a hydroxyl group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 alkoxy C1-C6 alkoxy group, a C1-C6 alkylthiothiocarbonyloxy group, or a C1-C6 haloalkylsulfonyloxy group, at least one of which is a substituent other than a hydrogen atom, and R ２ and R ３ two adjacent substituents, taken together with the carbons to which they are attached, form a 3- to 6-membered carbocyclic ring or a 3- to 6-membered heterocyclic ring having 1 to 4 heteroatoms independently selected from oxygen, sulfur and nitrogen atoms, wherein the ring formed optionally bears one or more substituents; X is an oxygen atom, CR ４ R ５ , or NR ６ represents R ４ and R ５ each independently represents a hydrogen atom or a C1-C6 alkyl group, R ６ represents a hydroxyl group, a C1-C6 alkyl group, a C1-C6 alkoxy group, an amino group, a C1-C6 alkylamino group, an aminocarbonylamino group, or a phenylamino group (which may be mono- or poly-substituted with a halogen atom, a C1-C6 alkyl group, or a C1-C6 haloalkyl group).

3. A synthetic intermediate represented by the following general formula (1a), (1a'), (2a) or (2a'), which is useful in producing the 1,4-cineole derivative represented by the general formula (1), (1'), (2) or (2') according to claim 1 or 2. 【Chemistry 2】 (In the general formulas (1a), (1a'), (2a) and (2a'), R １ａ each independently represents a hydrogen atom or a tri-C1-C6 alkylsilyl group, which may be the same or different. R ２ａ and R ３ａ each independently represents a hydrogen atom, a halogen atom, a hydroxyl group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 alkoxy-C1-C6 alkoxy group, a C1-C6 alkylcarbonyloxy group, a C1-C6 alkoxycarbonyloxy group, a C1-C6 alkylthiocarbonyloxy group, a C1-C6 alkylthiothiocarbonyloxy group, a C1-C6 alkylsulfonyloxy group, or a C1-C6 haloalkylsulfonyloxy group, and at least one of them is a substituent other than a hydrogen atom. ２ａ and R ３ａ two adjacent substituents, taken together with the carbons to which they are attached, form a 3- to 6-membered carbocyclic ring or a 3- to 6-membered heterocyclic ring having 1 to 4 heteroatoms independently selected from oxygen, sulfur, and nitrogen atoms, wherein the ring formed may have one or more substituents. X ａ is an oxygen atom, a sulfur atom, CR ４ａ R ５ａ , or NR ６ａ Represents. R ４ａ and R ５ａ each independently represents a hydrogen atom or a C1-C6 alkyl group. R ６ａ represents a hydrogen atom, a hydroxyl group, a C1-C6 alkyl group, a C1-C6 alkoxy group, an amino group, a C1-C6 alkylamino group, an aminocarbonylamino group, or a phenylamino group (which may be mono- or poly-substituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups).

4. R １ａ each independently represents a hydrogen atom or a tri-C1-C6 alkylsilyl group, which may be the same or different, R ２ａ and R ３ａ each independently represents a hydrogen atom, a halogen atom, a hydroxyl group, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 alkoxy C1-C6 alkoxy group, a C1-C6 alkylthiothiocarbonyloxy group, or a C1-C6 haloalkylsulfonyloxy group, at least one of which is a substituent other than a hydrogen atom, and R ２ａ and R ３ａ two adjacent substituents, taken together with the carbons to which they are attached, form a 3- to 6-membered carbocyclic ring or a 3- to 6-membered heterocyclic ring having 1 to 4 heteroatoms independently selected from oxygen, sulfur and nitrogen atoms, wherein the ring formed optionally bears one or more substituents; X ａ is an oxygen atom, CR ４ａ R ５ａ , or NR ６ａ represents R ４ａ and R ５ａ each independently represents a hydrogen atom or a C1-C6 alkyl group, R ６ａ represents a hydroxyl group, a C1-C6 alkyl group, a C1-C6 alkoxy group, an amino group, a C1-C6 alkylamino group, an aminocarbonylamino group, or a phenylamino group (which may be mono- or poly-substituted with halogen atoms, C1-C6 alkyl groups, or C1-C6 haloalkyl groups).

5. A herbicide containing the 1,4-cineole derivative according to claim 1 or 2 as an active ingredient.

6. The herbicide according to claim 5, which is for use on agricultural land, pasture, turf, or non-agricultural land.

7. 6. The method for using a herbicide according to claim 5, wherein an effective amount of the 1,4-cineole derivative is applied to at least one selected from the foliage of weeds, soil, and water surface.

8. 10. A method for preparing an agrochemical composition, comprising the step of mixing the herbicide of claim 5 with at least one selected from a filler and a surfactant.

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