Fluorine-containing isoxazole compound and method for producing the same

Abstract

The present invention relates to a fluorine-containing isoxazole compound represented by general formula (A). (In general formula (A), R represents a hydrogen atom or a substituted or unsubstituted C1-12 hydrocarbon group, X represents a halogen atom, -OA1, -O-NA1A2, -NA1A2, -NA1(OA2), -NA3-NA1A2, -NA4, or a heterocycle, A1, A2, and A3 each independently represent a substituted or unsubstituted C1-12 hydrocarbon group or a heterocycle, A4 represents an alkylene group represented by =CnH2n, n is an integer of 1-20, and Y1 and Y2 each independently represent N or O and are different from each other.)

Description

[Technical Field]

[0001] The present invention relates to a fluorine-containing isoxazole compound and a method for producing the same. [Background technology]

[0002] Compounds containing an isoxazole ring or its tautomer, an isoxazolone ring, are known to have various pharmacological effects, including natural products such as ibotenic acid and muscimol. Examples of pharmaceuticals include β-lactam antibiotics such as oxacillin and flucloxacillin, sulfonamide antibiotics such as sulfafurazole and sulfamethoxazole, oxazolidinone antibiotics such as posizolid, antirheumatic drugs such as leflunomide and valdecoxib, liver disease treatment drug such as tropifexor, anticancer drug such as tivozanib, antiviral drug such as pleconaril, antidepressant drug such as isocarboxazid, diabetes treatment drug such as glisoxepide, and endometriosis treatment drug such as danazol. Further, examples of pesticides include isoxathion as an insecticide, isoxaben as a herbicide, and the like.

[0003] Given the wide range of pharmacological actions of isoxazoles, there has been recent interest in introducing heteroatom substituents (substituents having a heteroatom) into positions 3 and / or 5. Specifically, Non-Patent Document 1 reports that compounds having an isoxazole ring substituted with a methoxy group at position 3 and a 1-tetrazolyl group at position 5 have cholinesterase inhibitory activity and are therefore being studied as therapeutic agents for Alzheimer's disease.

[0004] There is also interest in the pharmacological effects of compounds having a trifluoromethyl group at the 4-position of the isoxazole ring. Specifically, Non-Patent Document 2 reports that such compounds have agonistic activity of the sphingosine-1-phosphate receptor S1P1 and are therefore being studied as therapeutic agents for autoimmune diseases.

[0005] From this perspective, it is desirable to develop fluorine-containing isoxazole compounds that not only have heteroatom substituents at the 3- and / or 5-positions of the isoxazole ring, but also have a trifluoromethyl group at the 4-position of the isoxazole ring, in the hope of finding useful therapeutic agents for various diseases. [Prior art documents] [Non-patent literature]

[0006] [Non-Patent Document 1] New Journal of Chemistry, 2015, Vol. 39, pp. 2028-2041 [Non-patent document 2] Bioorganic & Medicinal Chemistry Letters, 2016, Vol. 26, pp. 2470-2474 Summary of the Invention [Problem to be solved by the invention]

[0007] Therefore, the present inventors discovered that by reacting specific raw materials, it is possible to construct a structure having a trifluoromethyl group at the 4-position on the isoxazole ring and substituted with a heteroatom substituent at the 3- and / or 5-position, and thus completed the present invention.

[0008] The present invention provides novel fluorine-containing isoxazole compounds having a trifluoromethyl group at the 4-position on the isoxazolone ring and a heteroatom substituent at the 3- and / or 5-position, and a production method that enables the simple production of the fluorine-containing isoxazole compounds. [Means for solving the problem]

[0009] The fluorine-containing isoxazole compound according to this embodiment is represented by the following general formula (A). [ka] (In the above general formula (A), R represents a hydrogen atom or a substituted or unsubstituted hydrocarbon having 1 to 12 carbon atoms; X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle, A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20, Y 1 and Y 2 each independently represents N or O and is different from each other.

[0010] The method for producing a fluorine-containing isoxazole compound according to this embodiment includes the steps of: (I) A method of reacting a fluorine-containing compound selected from a fluorine-containing carbonyl compound, a fluoroisobutene derivative, and a fluoroisobutane derivative with hydroxylamine or a salt thereof, and optionally with a compound represented by the following general formula (5) or a salt thereof, or (II) The method comprises a step of reacting a fluorine-containing compound selected from a fluorine-containing carbonyl compound, a fluoroisobutene derivative, and a fluoroisobutane derivative with an amine salt or an amine compound, and optionally with a compound represented by the following general formula (5) or a salt thereof, to synthesize a fluorine-containing isoxazole compound represented by the following general formula (A): [ka] (In the above general formulas (A) and (5), R represents a hydrogen atom or a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA 1 (OA 2 ), -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle, A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20, Y 1 and Y 2 each independently represents N or O and is different from each other. [Effects of the Invention]

[0011] Provided are novel fluorine-containing isoxazole compounds having a trifluoromethyl group at the 4-position on the isoxazolone ring and a heteroatom substituent at the 3- and / or 5-position, and a production method that enables the easy production of the fluorine-containing isoxazole compounds. DETAILED DESCRIPTION OF THE INVENTION

[0012] Hereinafter, embodiments of the present invention will be described in detail. However, the scope of the present invention is not limited to the specific examples described below. Furthermore, the heteroatom substituent is a substituent having a heteroatom, and refers to a functional group containing at least one heteroatom selected from the group consisting of a nitrogen atom (N), a sulfur atom (S), and an oxygen atom (O).

[0013] (Fluorine-containing isoxazole compound) The fluorine-containing isoxazole compound in this embodiment is represented by the following general formula (A), and has a trifluoromethyl group at the 4-position on the isoxazole ring and a heteroatom substituent at the 3-position and / or 5-position.

[0014] [ka] (In the above general formula (A), R represents a hydrogen atom or a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA 1 (OA 2 ), -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle, A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20, Y 1 and Y 2each independently represents N or O and is different from each other.

[0015] Y 1 N, Y 2 When is O and R is a hydrogen atom, the fluorine-containing isoxazole compound represented by general formula (A) is represented by the following general formula (1).

[0016] [ka] (In the above general formula (1), X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA 1 (OA 2 ), -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle, and A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20.

[0017] Y 1 N, Y 2 When is O and R is a hydrocarbon group having 1 to 12 carbon atoms, the fluorine-containing isoxazole compound represented by general formula (A) is represented by the following general formula (2).

[0018] [ka] (In the above general formula (2), R represents a substituted or unsubstituted hydrocarbon having 1 to 12 carbon atoms; X is a halogen atom, -OA 1, -O-NA 1 A 2 , -NA 1 A 2 , -NA 1 (OA 2 ), -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle, A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20.

[0019] Y 1 O, Y 2 When is N and R is a hydrogen atom, the fluorine-containing isoxazole compound represented by general formula (A) is represented by the following general formula (3).

[0020] [ka] (In the above general formula (3), X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA 1 (OA 2 ), -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle, A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A 4 =C n H 2nrepresents an alkylene group represented by the formula: n is an integer from 1 to 20.

[0021] Y 1 O, Y 2 When is N and R is a hydrocarbon group having 1 to 12 carbon atoms, the fluorine-containing isoxazole compound represented by general formula (A) is represented by the following general formula (4).

[0022] [ka] (In the above general formula (4), R' represents a substituted or unsubstituted hydrocarbon having 1 to 12 carbon atoms; X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA 1 (OA 2 ), -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle, A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20.

[0023] When R and R' are substituted or unsubstituted hydrocarbon groups having 1 to 12 carbon atoms, they are not particularly limited as long as they are hydrocarbon groups consisting of carbon atoms and hydrogen atoms having 1 to 12 carbon atoms, and examples thereof include chain hydrocarbon groups, aromatic hydrocarbon groups, and alicyclic hydrocarbon groups. The chain hydrocarbon groups are not particularly limited as long as they have a total of 1 to 12 carbon atoms, and may be linear or branched chain hydrocarbon groups, or may be substituted or unsubstituted chain hydrocarbon groups. When R and R' are aromatic hydrocarbon groups, they are not particularly limited as long as they have a total of 6 to 12 carbon atoms, and may be substituted or unsubstituted aromatic hydrocarbon groups. The aromatic hydrocarbon groups may also have a fused polycyclic structure. When R and R' are alicyclic hydrocarbon groups, they are not particularly limited as long as they have a total of 3 to 12 carbon atoms, and may be substituted or unsubstituted alicyclic hydrocarbon groups. The alicyclic hydrocarbon groups may also have a bridged ring structure.

[0024] Examples of the chain hydrocarbon group include alkyl groups such as a methyl group, an ethyl group, an n-propyl group, an i-propyl group, an n-butyl group, an i-butyl group, a sec-butyl group, a tert-butyl group, a pentyl group, a hexyl group, a heptyl group, an octyl group, a nonyl group, a decyl group, an undecyl group, and a dodecyl group; alkenyl groups such as ethenyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl, nonenyl, decenyl, undecenyl, and dodecenyl groups; Examples of the alkynyl group include ethynyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl, octynyl, nonynyl, decynyl, undecynyl, and dodecynyl groups.

[0025] Examples of the aromatic hydrocarbon group include a phenyl group and a naphthyl group.

[0026] Alicyclic hydrocarbon groups include saturated or unsaturated cyclic hydrocarbon groups, and examples of cyclic hydrocarbon groups include a cyclopropyl group, a cyclobutyl group, a cyclohexyl group, a cyclopentyl group, an adamantyl group, and a norbornyl group.

[0027] When the chain hydrocarbon group has a substituent, one of the hydrogen atoms of the chain hydrocarbon group may be substituted with an alkoxyl group or an aralkyl group. The alkoxyl group is preferably an alkoxyl group having 1 to 6 carbon atoms, such as a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a sec-butoxy group, a tet-butoxy group, an n-pentoxy group, or an n-hexyloxy group. The aralkyl group is preferably an alkyl group having 1 to 6 carbon atoms, such as a benzyl group, a phenylethyl group, a phenylpropyl group, or a naphthylmethyl group.

[0028] When the aromatic hydrocarbon group and the alicyclic hydrocarbon group have a substituent, examples of the substituent include the above-mentioned alkyl groups and alkoxyl groups having 1 to 6 carbon atoms.

[0029] In X, the halogen atom is F, Cl, Br or I, and is preferably F or Cl.

[0030] In X, -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA 1 (OA 2 ) and -NA 3 -NA 1 A 2 A included in 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms. 1 A 2 , -NA 1 A2 , -NA 1 (OA 2 ) or -NA 3 -NA 1 A 2 If A 1 , A 2 and A 3 may be the same or different. 1 , A 2 and A 3 When represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, A 1 , A 2 and A 3 is the same as the hydrocarbon group having 1 to 12 carbon atoms defined for R and R' above, and can be, for example, a hydrocarbon group having 1 to 12 carbon atoms among the above R and R'. The hydrocarbon group having 1 to 12 carbon atoms is preferably a chain hydrocarbon group having 1 to 12 carbon atoms, more preferably a chain hydrocarbon group having 1 to 10 carbon atoms, even more preferably an alkyl group having 1 to 10 carbon atoms, and particularly preferably an alkyl group having 1 to 4 carbon atoms.

[0031] In X, the heterocycle is an optionally substituted monocyclic, bicyclic, or polycyclic heterocycle containing at least one heteroatom selected from the group consisting of nitrogen (N), sulfur (S), and oxygen (O) atoms as a ring atom. The heterocyclic group may have multiple heteroatoms, which may be the same or different. Each heterocycle preferably contains at least one nitrogen atom as a heteroatom in its skeleton. One of the heteroatoms contained in the heterocyclic group, preferably N, is directly bonded to the isoxazole ring of the fluorine-containing isoxazole compound and is substituted on the isoxazole ring as a heteroatom substituent. The heterocycle may be a fused ring, an alicyclic heterocycle, an aromatic heterocycle, or a combination thereof.

[0032] The monocyclic heterocycle is preferably a 3- to 12-membered ring, and more preferably a 5- to 9-membered ring. When the heterocycle is a monocyclic heterocycle, it may contain up to five heteroatoms. Each heteroatom is individually selected from O, S, and N, and it is preferable that at least one of the heteroatoms is N. Examples of monocyclic heterocycles include pyrrolidine, pyrroline, pyrrole, pyrazolidine, imidazolidine, pyrazoline, imidazoline, imidazole, pyrazole, triazole, tetrazole, (iso)oxazole, (iso)oxadiazole, (iso)thiazole, thiadiazole, pyridine, pyrrolidine, piperidine, piperazine, pyridazine, pyrimidine, pyrazine, triazine, thienopyridine, piperazinone, morpholine, thiomorpholine, thiomorpholine dioxide, oxazine, thiazine, azocane, azocine, azonane, azonine, and derivatives thereof.

[0033] The bicyclic heterocycle is preferably a 7- to 14-membered ring, and more preferably an 8- to 10-membered ring. The bicyclic heterocycle may also contain a spiro ring. When the heterocycle is a bicyclic heterocycle, it may contain up to 10 heteroatoms. Each heteroatom is independently selected from O, S, and N, and it is preferred that at least one of the heteroatoms is N. Examples of bicyclic heterocycles include (iso)indole, aza(iso)indole, (aza)indazole, (aza)benzimidazole, (aza)benztriazole, hydrothienopyridine, (iso)quinoline, hydro(iso)quinoline, hydrofuropyridine, and derivatives thereof.

[0034] The polycyclic heterocycle is preferably a 9- to 30-membered ring, and more preferably a 12- to 26-membered ring. The polycyclic heterocycle may also contain a spiro ring. When the heterocycle is a polycyclic heterocycle, it may contain up to 15 heteroatoms. Each heteroatom is independently selected from O, S, and N, and it is preferred that at least one of the heteroatoms is N. Examples of polycyclic heterocycles include carbazole, phenazine, phenoxazine, phenothiazine, benzoindole, pyrroloquinoline, acridine, and derivatives thereof.

[0035] When the heterocycle has a substituent, the substituent may be a halogen atom, a C1-C 10 Examples of the substituents include hydrocarbon groups, oxygen-containing substituents such as hydroxyl groups, alkoxy groups, carbonyl groups, and carboxyl groups, nitrogen-containing substituents such as amino groups, cyano groups, and nitro groups, and sulfur-containing substituents such as sulfanyl groups, sulfoxy groups, and sulfone groups.

[0036] A 1 , A 2 and A 3 When is a heterocycle, A 1 , A 2 and A 3 is the same as the heterocycle defined above for X. 1 A 2 or -NA 1 A 2 If A 1 A is a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; 2 may be a heterocycle. 1 (OA 2 ), then A 1 A is a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; 2 may be a heterocycle, and A 1 is a heterocycle, A 2 may be a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms. 3 -NA 1 A 2 If A 1 and A 3A is a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; 2 may be a heterocycle, and A 1 A is a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; 2 and A 3 may be a heterocycle.

[0037] In X, -NA 4 A included in 4 =C n H 2n where n is an integer of 1 to 20. n H 2n The alkylene group represented by the following formula may be linear or may have a branched structure. n is preferably 3 to 15, and more preferably 5 to 10.

[0038] The fluorine-containing isoxazole compound of this embodiment has a specific substituent (-X, -CF3, -OR, or -OR') on the isoxazole ring, which can provide excellent structural expandability, and is particularly expected to further enhance pharmacological activity. Furthermore, since the 3-, 4-, and 5-positions on the isoxazole ring can each have a different substituent, the compound can be easily derivatized to an asymmetric structure, and its use as an intermediate is also expected. More specifically, a derivative can be obtained by modifying -OR or -OR' by reacting the fluorine-containing isoxazole compound under acidic conditions. Furthermore, when the substituent X on the isoxazole ring is a halogen atom, a derivative can be obtained by modifying the halogen atom by reacting the fluorine-containing isoxazole compound under basic conditions. Furthermore, the fluorine-containing isoxazole compound of this embodiment is also useful in the fields of electronic materials, such as organic semiconductors and liquid crystals.

[0039] (Method of producing fluorine-containing isoxazole compound) The method for producing a fluorine-containing isoxazole compound in this embodiment includes the steps of: (I) generating a fluorine-containing isoxazole compound selected from the group consisting of a fluorine-containing carbonyl compound, a fluoroisobutene derivative, and a fluoroisobutane derivative; IncludingThe method includes a step of reacting a fluorine-containing compound, hydroxylamine or a salt thereof, and optionally a compound represented by the following general formula (5) or a salt thereof, to synthesize a fluorine-containing isoxazole compound represented by general formula (A) by reacting a fluorine-containing compound selected from fluorine-containing carbonyl compounds, fluoroisobutene derivatives, and fluoroisobutane derivatives with an amine salt or an amine compound, and optionally a compound represented by the following general formula (5) or a salt thereof:

[0040] [ka] (In the above general formulas (A) and (5), R represents a hydrogen atom or a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA 1 (OA 2 ), -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle, A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20, Y 1 and Y 2 each independently represents N or O and is different from each other.

[0041] Such a fluorine-containing isoxazole compound represented by the general formula (A) can be synthesized, for example, by the following method.

[0042] A first embodiment of the present invention for producing a fluorinated isoxazole compound includes (a) a step of reacting a fluorinated carbonyl compound represented by the following general formula (6) with a hydroxylamine represented by the following general formula (7) or a salt thereof to obtain a fluorinated isoxazole compound represented by the following general formula (1): [ka] (In the above general formulas (1) and (6), X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA 1 (OA 2 ), -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle, Z is -OA 5 , -O-NA 5 A 6 , -NA 5 A 6 , -NA 5 (OA 6 ) or -NA 7 -NA 5 A 6 represents A 1 , A 2 and A 3 are each independently a substituted or unsubstituted alkyl group having 1 to 12 carbon atoms. represents a hydrocarbon group or heterocycle represented by the formula: A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20, A 5 , A 6 and A 7 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; The wavy bond indicates a single bond, representing either (E) or (Z) stereoisomerism.)

[0043] A second embodiment of the present invention for producing a fluorinated isoxazole compound includes (b) a step of reacting a fluorinated carbonyl compound represented by the following general formula (8), a compound represented by the following general formula (5) or a salt thereof, and a hydroxylamine represented by the following general formula (7) or a salt thereof to obtain a fluorinated isoxazole compound represented by the following general formula (1): [ka] (In the above general formulas (1), (5) and (8), X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA 1 (OA 2 ), -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle, Z is -OA 5 , -O-NA 6 A 7 , -NA 5 A 6 , -NA 5 (OA 6 ) or -NA 7 -NA 5 A 6 represents A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20, A 5 , A 6 and A 7each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.

[0044] A third embodiment of the present invention for producing a fluorine-containing isoxazole compound includes (c) a step of reacting a fluorine-containing carbonyl compound represented by the following general formula (9) with a compound represented by the following general formula (5) or a salt thereof in the presence of a base, and then further reacting the resulting reaction product with a hydroxylamine represented by the following general formula (7) or a salt thereof to obtain a fluorine-containing isoxazole compound represented by the following general formula (1): [ka] (In the above general formulas (1), (5) and (9), X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA 1 (OA 2 ), -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle, Z is -OA 5 , -O-NA 6 A 7 , -NA 5 A 6 , -NA 5 (OA 6 ) or -NA 7 -NA 5 A 6 represents A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20, A 5 , A6 and A 7 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.

[0045] A fourth embodiment of the present invention for producing a fluorine-containing isoxazole compound includes (d) a step of reacting a fluorine-containing carbonyl compound represented by the following general formula (10) with an alcohol, reacting the resulting reaction product with a compound represented by the following general formula (5) in the presence of a base, and then reacting the resulting reaction product with hydroxylamine represented by the following general formula (7) or a salt thereof to obtain a fluorine-containing isoxazole compound represented by the following general formula (1): [ka] (In the above general formulas (1), (5) and (10), X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA 1 (OA 2 ), -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle, A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20, W + represents an ammonium cation, an imidazolium cation, a pyridinium cation, a quinuclidium cation, or a phosphonium cation.

[0046] A fifth embodiment of the present invention for producing a fluorinated isoxazole compound includes the steps of (e) carbonylating a fluoroisobutene derivative represented by the following general formula (11) in the presence of a nucleophile, further reacting the resulting reaction product with an alcohol, reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof in the presence of a base, and then reacting the resulting reaction product with hydroxylamine represented by the following general formula (7) or a salt thereof to obtain a fluorinated isoxazole compound represented by the following general formula (1): [ka] (In the above general formulas (1), (5) and (11), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA 1 (OA 2 ), -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle, A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20.

[0047] A sixth embodiment of the present invention for producing a fluorine-containing isoxazole compound includes the steps of (f) carbonylating a compound obtained by an elimination reaction of a fluoroisobutane derivative represented by the following general formula (12) in the presence of a nucleophile, further reacting with an alcohol, and then reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof in the presence of a base, and then reacting with hydroxylamine represented by the following general formula (7) or a salt thereof to obtain a fluorine-containing isoxazole compound represented by the following general formula (1): [ka] (In the above general formulas (1), (5) and (12), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA 1 (OA 2 ), -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle, Y is a halogen atom, -OB 1 , -SO m B 1 or -NB 1 B 2 represents m is an integer from 0 to 3, A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20, B 1 and B 2each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.

[0048] A seventh embodiment of the present embodiment for producing a fluorinated isoxazole compound includes (g) a step of reacting a fluorinated carbonyl compound represented by the following general formula (13) with an amine salt or an amine compound to obtain a fluorinated isoxazole compound represented by the following general formula (2): [ka] (In the above general formulas (2) and (13), R represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X is -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA 1 (OA 2 ), -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle, A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20, The wavy bond indicates a single bond, representing either (E) or (Z) stereoisomerism.)

[0049] An eighth embodiment of the present invention for producing a fluorinated isoxazole compound includes (h) a step of reacting a fluorinated carbonyl compound represented by the following general formula (14), an amine salt or an amine compound, and, optionally, a compound represented by the following general formula (5) or a salt thereof, to obtain a fluorinated isoxazole compound represented by the following general formula (2): [ka] (In the above general formulas (2) and (14), R represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 (OA 2 ), -NA 1 A 2 , -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle, A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20.

[0050] A ninth embodiment of the present embodiment for producing a fluorinated isoxazole compound includes (i) a step of reacting a fluorinated carbonyl compound represented by the following general formula (15) with a compound represented by the following general formula (5) or a salt thereof in the presence of a base, and then reacting the resulting reaction product with an amine salt or an amine compound to obtain a fluorinated isoxazole compound represented by the following general formula (2): [ka] (In the above general formulas (2), (5) and (15), R represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 A 2, -NA 1 (OA 2 ), -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle, A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20.

[0051] A tenth embodiment of the present invention for producing a fluorinated isoxazole compound includes (j) a step of reacting a fluorinated carbonyl compound represented by the following general formula (10) with an alcohol, reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof in the presence of a base, and then reacting the resulting reaction product with an amine salt or an amine compound to obtain a fluorinated isoxazole compound represented by the following general formula (2): [ka] (In the above general formulas (2), (5) and (10), R represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA 1 (OA 2 ), -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle, A 1 , A 2 and A 3each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20, W + represents an ammonium cation, an imidazolium cation, a pyridinium cation, a quinuclidium cation, or a phosphonium cation.

[0052] An eleventh embodiment of the present embodiment for producing a fluorinated isoxazole compound includes a step of (k) carbonylating a fluoroisobutene derivative represented by the following general formula (11) in the presence of a nucleophile, further reacting the resulting reaction product with an alcohol, reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof in the presence of a base, and then reacting the resulting reaction product with an amine salt or an amine compound, thereby obtaining a fluorinated isoxazole compound represented by the following general formula (2): [ka] (In the above general formulas (2), (5) and (11), R and R' each independently represent a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA 1 (OA 2 ), -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle, A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; A 4 =C n H2n represents an alkylene group represented by the formula: n is an integer from 1 to 20.

[0053] A twelfth embodiment of the present embodiment for producing a fluorine-containing isoxazole compound comprises: (l) a step of carbonylating a compound obtained by an elimination reaction of a fluoroisobutane derivative represented by the following general formula (12) in the presence of a nucleophile, further reacting the resulting reaction product with an alcohol, reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof in the presence of a base, and then reacting the resulting reaction product with an amine salt or an amine compound, thereby obtaining a fluorine-containing isoxazole compound represented by the following general formula (2): [ka] (In the above general formulas (2), (5) and (12), R and R' each independently represent a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA 1 (OA 2 ), -NA 3 -NA 1 A 2 -NA 4 or a heterocycle, Y is a halogen atom, -OB 1 , -SO m B 1 or -NB 1 B 2 represents m is an integer from 0 to 3, A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20, B 1 and B 2 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.

[0054] A thirteenth embodiment of the present embodiment for producing a fluorinated isoxazole compound includes a step (m) of reacting a fluorinated carbonyl compound represented by the following general formula (10) with a hydroxylamine represented by the following general formula (7) or a salt thereof, and further reacting the obtained reaction product with a compound represented by the following general formula (5) or a salt thereof to obtain a fluorinated isoxazole compound represented by the following general formula (3): [ka] (In the above general formulas (3), (5) and (10), X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA 1 (OA 2 ), -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle, A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20, W + represents an ammonium cation, an imidazolium cation, a pyridinium cation, a quinuclidium cation, or a phosphonium cation.

[0055] A fourteenth embodiment of the present invention for producing a fluorinated isoxazole compound includes (n) a step of carbonylating a fluoroisobutene derivative represented by the following general formula (11) in the presence of a nucleophile, further reacting the fluoroisobutene derivative with a hydroxylamine represented by the following general formula (7) or a salt thereof, and then reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof to obtain a fluorinated isoxazole compound represented by the following general formula (3): [ka] (In the above general formulas (3), (5) and (11), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA 1 (OA 2 ), -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle, A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20.

[0056] A fifteenth embodiment of the present invention for producing a fluorinated isoxazole compound includes (o) a step of carbonylating a fluoroisobutane derivative represented by the following general formula (12) in the presence of a nucleophile, further reacting the carbonylation with a hydroxylamine represented by the following general formula (7) or a salt thereof, and then reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof to obtain a fluorinated isoxazole compound represented by the following general formula (3): [ka] (In the above general formulas (3), (5) and (12), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA 1 (OA 2 ), -NA 3 -NA 1 A 2 -NA 4 or a heterocycle, Y is a halogen atom, -OB 1 , -SO m B 1 or -NB 1 B 2 represents m is an integer from 0 to 3, A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20, B 1 and B 2 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.

[0057] A 16th embodiment of the present embodiment for producing a fluorinated isoxazole compound includes (p) a step of reacting a fluoroisobutene derivative represented by the following general formula (11), a compound represented by the following general formula (5) or a salt thereof, and a hydroxylamine represented by the following general formula (7) or a salt thereof to obtain a fluorinated isoxazole compound represented by the following general formula (4): [ka] (In the above general formulas (4), (5) and (11), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 (OA 2 ), -NA 1 A 2 , -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle, A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20.

[0058] A seventeenth embodiment of the present embodiment for producing a fluorinated isoxazole compound includes (q) a step of reacting a fluoroisobutene derivative represented by the following general formula (11) with a hydroxylamine represented by the following general formula (7) or a salt thereof to obtain a fluorinated isoxazole compound represented by the following general formula (4-1): [ka] (In the above general formulas (4-1) and (11), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.

[0059] An 18th embodiment of the present embodiment for producing a fluorinated isoxazole compound includes a step (r) of reacting a fluoroisobutane derivative represented by the following general formula (12), a compound represented by the following general formula (5) or a salt thereof, and a hydroxylamine represented by the following general formula (7) or a salt thereof to obtain a fluorinated isoxazole compound represented by the following general formula (4): [ka] (In the above general formulas (4), (5) and (12), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA 1 (OA 2 ), -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle, and Y is a halogen atom, -OB 1 , -SO m B 1 or -NB 1 B 2 represents m is an integer from 0 to 3, A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20, B 1 and B 2 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.

[0060] A 19th embodiment of the present embodiment for producing a fluorinated isoxazole compound includes (s) a step of reacting a fluoroisobutane derivative represented by the following general formula (12) with a hydroxylamine represented by the following general formula (7) or a salt thereof to obtain a fluorinated isoxazole compound represented by the following general formula (4-1): [ka] (In the above general formulas (4-1) and (12), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; Y is a halogen atom, -OB 1 , -SO m B 1 or -NB 1 B 2 represents m is an integer from 0 to 3, B 1 and B 2 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.

[0061] In the fluorine-containing compounds, the fluorine-containing carbonyl compound is preferably a compound represented by the above general formula (6), (8), (9), (10), (13), (14) or (15), the fluoroisobutene derivative is preferably a compound represented by the above general formula (11), and the fluoroisobutane derivative is preferably a compound represented by the above general formula (12).

[0062] In the above general formulas (5), (6), and (13), A 1 , A 2 , A 3and heterocycle are the same as those defined in the fluorine-containing isoxazole compounds represented by the above general formulae (A) and (1) to (4). In the above general formulae (4-1), (11), and (12), R' is the same as that defined in the fluorine-containing isoxazole compound represented by the above general formula (4), and the substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms in R' is preferably an alkyl group having 1 to 10 carbon atoms.

[0063] In the above general formulas (6), (8), and (9), A 5 , A 6 and A 7 is the same as the substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms defined above for R and R', and A 5 , A 6 and A 7 The substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms in the formula (I) is preferably an alkyl group having 1 to 10 carbon atoms.

[0064] In the above general formula (12), B 1 and B 2 is the same as the substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms defined above for R and R'.

[0065] In each of the above general formulas (12), Y is a halogen atom, -OB 1 , -SO m B 1 or -NB 1 B 2 Represents.

[0066] In Y, the halogen atom is F, Cl, Br or I, and is preferably F or Cl.

[0067] In Y, -OB 1 , -SO m B 1 B included in 1represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, and is the same as the hydrocarbon group having 1 to 12 carbon atoms defined above for R and R'. Furthermore, m is an integer of 0 to 3, preferably an integer of 0 to 2, and more preferably an integer of 0 to 1.

[0068] In Y, -NB 1 B 2 B included in 1 and B 2 are each independently a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms. 1 and B 2 may be the same or different. B 1 and B 2 is the same as the hydrocarbon group having 1 to 12 carbon atoms defined above for R and R'.

[0069] The reaction (a) in the first embodiment is represented as the following reaction formula (A) as a whole. [ka]

[0070] The reaction (b) in the second embodiment is represented as the following reaction formula (B) as a whole. [ka]

[0071] The reaction (c) in the third embodiment is represented as the following reaction formula (C) as a whole. [ka]

[0072] The reaction (d) in the fourth embodiment is expressed as the following reaction formula (D): In the following reaction formula, "WF" represents the cation W + and F - It represents salt of. [ka]

[0073] The reaction (e) in the fifth embodiment is expressed as the following reaction formula (E) as a whole. In the following reaction formula, the nucleophile may be represented as "Nu" for convenience. Furthermore, "NuR'F" represents the reaction of the cation of the nucleophile with R' substituted with F. - It represents salt of. [ka]

[0074] The reaction (f) in the sixth embodiment is represented as the following reaction formula (F) as a whole. [ka]

[0075] The reaction (g) in the seventh embodiment is represented as a whole by the following reaction formula (G): In the following reaction formulas (G) to (O), the amine salt or amine compound may be referred to as "N compound" for convenience. [ka]

[0076] The reaction (h) in the eighth embodiment is represented as a whole by the following reaction formula (H): When the compound represented by general formula (5) or a salt thereof is not used in the reaction (h), X represents a fluorine atom (F) in the fluorine-containing isoxazole compound represented by general formula (2). [ka]

[0077] The reaction (i) in the ninth embodiment is represented as the following reaction formula (I) as a whole. [ka]

[0078] The reaction (j) in the tenth embodiment is represented as the following reaction formula (J) as a whole. [ka]

[0079] The reaction (k) in the eleventh embodiment is represented as the following reaction formula (K) as a whole. [ka]

[0080] The reaction (l) in the twelfth embodiment is represented as the following reaction formula (L) as a whole. [ka]

[0081] The reaction (m) in the thirteenth embodiment is represented as the following reaction formula (M) as a whole. [ka]

[0082] The reaction (n) in the fourteenth embodiment is represented as the following reaction formula (N) as a whole. [ka]

[0083] The above reaction (o) in the fifteenth embodiment is represented as the following reaction formula (O) as a whole. [ka]

[0084] The reaction (p) in the sixteenth embodiment is expressed as the following reaction formula (P) as a whole. [ka]

[0085] The reaction (q) in the seventeenth embodiment is represented as the following reaction formula (Q) as a whole. [ka]

[0086] The reaction (r) in the eighteenth embodiment is represented as the following reaction formula (R) as a whole. [ka]

[0087] The above reaction (s) in the nineteenth embodiment is represented as the following reaction formula (S) as a whole. [ka]

[0088] In each of the above reactions, the hydroxylamine represented by the general formula (7) and the compound represented by the general formula (5) may each be in the form of a salt. When the hydroxylamine represented by the general formula (7) is in the form of a salt, the portion (-NH2) constituting the amino group of the hydroxylamine is cationized to form (-NH3 + ) and forms a salt with the counter ion. When the compound represented by general formula (5) is in the form of a salt, the H moiety of the compound is cationized to form (H + ) and forms a salt with the counter ion. The counter ion is not particularly limited as long as it is a monovalent anion, and examples thereof include F - , Cl - , Br - , I -and the like, trifluoroacetate anion, paratoluenesulfonate anion, trifluoromethanesulfonate anion, nonafluorobutanesulfonic acid, bis(trifluoromethylsulfonyl)imide anion, tetrafluoroborate anion, and the like.

[0089] When an amine salt or an amine compound is used in each of the above reactions, examples of the amine salt and amine compound include amine salts of a nitrogen-containing heterocyclic cation in which one amino group (-NH2) is bonded to a nitrogen atom in the heterocycle or a quaternary ammonium cation in which one amino group (-NH2) is bonded to a nitrogen atom, and an anion selected from halogens, sulfuric acid, phosphoric acid, sulfonic acid, trifluoroacetic acid, tetrafluoroborate, tetraphenylborate, hexafluoroborate, and sulfonylimide acid; primary amines, hydroxylamines, or amine salts having an anionic substituent or anion selected from halogens, sulfuric acid, phosphoric acid, sulfonic acid, and trifluoroacetic acid; or quaternary ammonium salts substituted with a hydrocarbon group selected from alkyl groups and aryl groups.

[0090] In the nitrogen-containing heterocyclic cation, at least one nitrogen atom is contained as a heteroatom in the heterocycle, and may be optionally substituted. Furthermore, it is preferable that the nitrogen atom on the nitrogen-containing heterocycle is directly bonded to one amino group (—NH2), and the nitrogen-containing heterocyclic cation is a monocyclic heterocycle. The nitrogen-containing heterocycle may further contain at least one heteroatom selected from the group consisting of a nitrogen atom, a sulfur atom, and an oxygen atom (O) as a ring-constituting atom. The nitrogen-containing heterocycle is preferably an aromatic heterocycle, and the number of ring members is preferably 5 to 8, and more preferably 5 or 6. Examples of such nitrogen-containing heterocycles include pyridine, 4-dimethylaminopyridine, and 1-methylimidazole.

[0091] In a quaternary ammonium cation having one amino group (—NH2) bonded to a nitrogen atom, the nitrogen atom of the quaternary ammonium cation is preferably bonded to a hydrocarbon group selected from an alkyl group and an aryl group as another substituent. The alkyl group preferably has 1 to 12 carbon atoms and may be linear or branched. Examples of such alkyl groups include methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, and dodecyl groups. The aryl group preferably has 6 to 12 carbon atoms and may be substituted with a methyl group or the like. Examples of such aryl groups include tolyl and mesityl groups.

[0092] In the primary amine, hydroxylamine, or amine salt having the above-mentioned anionic substituent or anion, it is preferred that the anionic substituent or anion is directly bonded to the nitrogen atom constituting the amine. L It is preferred that an anionic substituent or an anion is directly bonded to the oxygen atom (-O-NH2) that constitutes the amine.

[0093] In the quaternary ammonium salt, the nitrogen atom of the quaternary ammonium salt is substituted with a hydrocarbon group selected from an alkyl group and an aryl group, and is not bonded to the amino group (—NH2). The alkyl group preferably has 1 to 12 carbon atoms and may be linear or branched. Examples of such alkyl groups include methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, and dodecyl groups. The aryl group preferably has 6 to 12 carbon atoms and may be substituted with methyl or the like. Examples of such aryl groups include tolyl and mesityl groups.

[0094] Specific examples of amine salts and amine compounds include 1-aminopyridinium iodide, tetrabutylammonium azide, hydroxylamine-O-sulfonic acid, 1-aminopyridinium mesitylenesulfonate, O-(mesitylenesulfonyl)hydroxylamine, 1,1,1-trimethylhydrazinium trifluoroacetate, and the like.

[0095] When a nucleophile is used in each of the above reactions, examples of the nucleophile include tertiary amines such as triethylamine, quinuclidine, and 1,4-diazabicyclo[2.2.2]octane, imidazole derivatives such as 1-methylimidazole, and pyridine derivatives such as pyridine and 4-dimethylaminopyridine.

[0096] When a base is used in each of the above reactions, examples of the base include inorganic compounds such as sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, sodium fluoride, and potassium fluoride; organic nitrogen derivatives such as pyridine, triethylamine, diisopropylethylamine, diazabicyclononene, diazabicycloundecene, methyltriazabicyclodecene, and diazabicyclooctane; and phosphorus derivatives such as phosphazene bases.

[0097] In each of the above reactions, when an alcohol (ROH) is used, the type of alcohol is not particularly limited as long as it can form an ester of the alcohol with 3,3,3-trifluoro-2-(trifluoromethyl)propanoic acid, and can be appropriately used depending on the desired structure of isoxazole.

[0098] When hydrogen fluoride (HF) is generated in the method for producing a fluorinated isoxazole compound according to the present embodiment, for example, a hydrogen halide scavenger may be used. By using the hydrogen halide scavenger, the step of recovering hydrogen fluoride can be omitted, and the fluorinated isoxazole compound represented by the general formula (A) can be obtained more simply.

[0099] In the above reaction (a), a cyclic isoxazole structure is formed between the fluorine-containing carbonyl compound represented by general formula (6) and the amino group of the hydroxylamine represented by general formula (7). X and CF of the fluorine-containing carbonyl compound represented by general formula (6) are located at the 3-position and the 4-position of the formed isoxazole structure, respectively, and OH formed due to the formation of the ring structure is located at the 5-position of the isoxazole structure.

[0100] In the above reaction (b), a cyclic isoxazole structure is formed between the fluorine-containing carbonyl compound represented by general formula (8) and the amino group of the hydroxylamine represented by general formula (7), the compound represented by general formula (5) is substituted at the 3-position of the isoxazole structure, and OH formed as a result of the formation of the ring structure is located at the 5-position of the isoxazole structure. CF3 possessed by the fluorine-containing carbonyl compound represented by general formula (8) is located at the 4-position of the formed isoxazole structure.

[0101] In the above reaction (c), a cyclic isoxazole structure is formed between the reaction product obtained by reacting a fluorine-containing carbonyl compound represented by general formula (9) with a compound represented by general formula (5) in the presence of a base and the amino group of the hydroxylamine represented by general formula (7), the compound represented by general formula (5) is substituted at the 3-position of the isoxazole structure, and OH formed as a result of the formation of the ring structure is located at the 5-position of the isoxazole structure. CF3 possessed by the fluorine-containing carbonyl compound represented by general formula (9) is located at the 4-position of the formed isoxazole structure.

[0102] In the above reaction (d), a cyclic isoxazole structure is formed between the reaction product obtained by reacting an intermediate reactant, obtained by reacting a fluorine-containing carbonyl compound represented by general formula (10) with an alcohol, and a compound represented by general formula (5) in the presence of a base, and the amino group of hydroxylamine represented by general formula (7), and the compound represented by general formula (5) is substituted at the 3-position of the isoxazole structure, and OH formed as a result of the formation of the ring structure is located at the 5-position of the isoxazole structure. CF3 possessed by the fluorine-containing carbonyl compound represented by general formula (10) is located at the 4-position of the formed isoxazole structure.

[0103] In the above reaction (e), a fluoroisobutene derivative represented by general formula (11) is carbonylated in the presence of a nucleophile, and then reacted with an alcohol to obtain an intermediate reactant. The intermediate reactant is then reacted with a compound represented by general formula (5) in the presence of a base to form a cyclic isoxazole structure between the reaction product and the amino group of hydroxylamine represented by general formula (7). The compound represented by general formula (5) is substituted at the 3-position of the isoxazole structure, and the OH formed as a result of the formation of the ring structure is located at the 5-position of the isoxazole structure. CF3 of the fluoroisobutene derivative represented by general formula (11) is located at the 4-position of the formed isoxazole structure.

[0104] In the above reaction (f), a compound obtained by an elimination reaction of a fluoroisobutane derivative represented by general formula (12) is carbonylated in the presence of a nucleophile, and further reacted with an alcohol to obtain an intermediate reactant, which is then reacted with a compound represented by general formula (5) in the presence of a base to form a reaction product between the compound and the amino group of hydroxylamine represented by general formula (7), and a cyclic isoxazole structure is formed between the compound represented by general formula (5) at the 3-position of the isoxazole structure, and the OH formed as a result of the formation of the ring structure is located at the 5-position of the isoxazole structure. CF3 of the fluorine-containing carbonyl compound represented by general formula (12) is located at the 4-position of the formed isoxazole structure.

[0105] In the above reaction (g), a cyclic isoxazole structure is formed between the fluorine-containing carbonyl compound represented by general formula (13) and the amino group of the amine salt or amine compound. X, CF3, and OR contained in the fluorine-containing carbonyl compound represented by general formula (13) are located at the 3-, 4-, and 5-positions of the formed isoxazole structure, respectively.

[0106] In the above reaction (h), a cyclic isoxazole structure is formed between the fluorine-containing carbonyl compound represented by general formula (14) and the amino group of the amine salt or amine compound. CF3 and OR contained in the fluorine-containing carbonyl compound represented by general formula (14) are located at the 4th and 5th positions of the formed isoxazole structure, respectively. When the fluorine-containing carbonyl compound represented by general formula (14) is further reacted with the compound represented by general formula (5), the compound represented by general formula (5) is substituted at the 3rd position of the isoxazole structure. When the compound represented by general formula (5) is not used, F contained in the fluorine-containing carbonyl compound represented by general formula (14) is located at the 3rd position of the isoxazole structure.

[0107] In the above reaction (i), a fluorine-containing carbonyl compound represented by general formula (15) is reacted with a compound represented by general formula (5) in the presence of a base to form a cyclic isoxazole structure between the reaction product and the amino group of the amine salt or amine compound, and the compound represented by general formula (5) is substituted at the 3-position of the isoxazole structure. CF3 and OR contained in the fluorine-containing carbonyl compound represented by general formula (15) are located at the 4- and 5-positions of the formed isoxazole structure, respectively.

[0108] In the above reaction (j), a cyclic isoxazole structure is formed between the reaction product obtained by reacting an intermediate reactant, obtained by reacting a fluorine-containing carbonyl compound represented by general formula (10) with an alcohol, and a compound represented by general formula (5) in the presence of a base, and the amino group of the amine salt or amine compound, and the compound represented by general formula (5) is substituted at the 3-position of the isoxazole structure. CF3 possessed by the fluorine-containing carbonyl compound represented by general formula (10) is located at the 4-position of the formed isoxazole structure. OR possessed by the intermediate reactant obtained by reacting a fluorine-containing carbonyl compound represented by general formula (10) with an alcohol (ROH) is located at the 5-position of the isoxazole structure.

[0109] In the above reaction (k), a fluoroisobutene derivative represented by general formula (11) is carbonylated in the presence of a nucleophile, and then reacted with an alcohol to obtain an intermediate reactant. This intermediate reactant is then reacted with a compound represented by general formula (5) in the presence of a base to form a cyclic isoxazole structure between the reaction product and the amino group of the amine salt or amine compound, and the compound represented by general formula (5) is substituted at the 3-position of the isoxazole structure. CF3 contained in the fluorine-containing carbonyl compound represented by general formula (11) is located at the 4-position of the formed isoxazole structure. OR contained in the intermediate reactant obtained by reacting the compound obtained by carbonylating the fluoroisobutene derivative represented by general formula (11) with an alcohol (ROH) is located at the 5-position of the isoxazole structure.

[0110] In the above reaction (l), a compound obtained by an elimination reaction of a fluoroisobutane derivative represented by general formula (12) is carbonylated in the presence of a nucleophile, and further reacted with an alcohol to obtain an intermediate reactant. This intermediate reactant is then reacted with a compound represented by general formula (5) in the presence of a base to form a cyclic isoxazole structure between the reaction product and the amino group of an amine salt or amine compound, and the compound represented by general formula (5) is substituted at the 3-position of the isoxazole structure. CF3 from the fluorine-containing carbonyl compound represented by general formula (12) is located at the 4-position of the formed isoxazole structure. OR from the intermediate reactant obtained by reacting the compound obtained by elimination reaction of a fluoroisobutene derivative represented by general formula (12) and further carbonylation with an alcohol (ROH) is located at the 5-position of the isoxazole structure.

[0111] In the above reaction (m), a cyclic isoxazole structure is formed between the fluorine-containing carbonyl compound represented by general formula (10) and the amino group of the hydroxylamine represented by general formula (7). The compound represented by general formula (5) is substituted at the 3-position of the isoxazole structure, and the OH formed as a result of the formation of the ring structure is located at the 5-position of the isoxazole structure. CF3 possessed by the fluorine-containing carbonyl compound represented by general formula (10) is located at the 4-position of the formed isoxazole structure.

[0112] In the above reaction (n), a fluoroisobutene derivative represented by general formula (11) is carbonylated in the presence of a nucleophile, and then reacted with an alcohol to obtain an intermediate reactant. The intermediate reactant is then reacted with a compound represented by general formula (5) in the presence of a base to obtain a reaction product, which is then combined with the amino group of hydroxylamine represented by general formula (7) to form a cyclic isoxazole structure. The compound represented by general formula (5) is substituted at the 3-position of the isoxazole structure, and the OH formed as a result of the formation of the ring structure is located at the 5-position of the isoxazole structure. CF3 from the fluoroisobutene derivative represented by general formula (11) is located at the 4-position of the formed isoxazole structure.

[0113] In the above reaction (o), a compound obtained by an elimination reaction of a fluoroisobutane derivative represented by general formula (12) is carbonylated in the presence of a nucleophile, and then further reacted with an alcohol to obtain an intermediate reactant. This intermediate reactant is then reacted with a compound represented by general formula (5) in the presence of a base to obtain a reaction product, which then forms a cyclic isoxazole structure between the amino group of hydroxylamine represented by general formula (7). The compound represented by general formula (5) is substituted at the 3-position of the isoxazole structure, and the OH formed as a result of the formation of the ring structure is located at the 5-position of the isoxazole structure. CF3 from the fluoroisobutene derivative represented by general formula (12) is located at the 4-position of the formed isoxazole structure.

[0114] In the reaction (p) above, a cyclic isoxazole structure is formed between the fluoroisobutylene derivative represented by general formula (11) and the amino group of the hydroxylamine represented by general formula (7), and the compound represented by general formula (5) is then substituted onto the isoxazole structure. —OR′ and CF3 from the fluoroisobutylene derivative are located at the 3rd and 4th positions, respectively, of the formed isoxazole structure, and X from the compound represented by general formula (5) is located at the 5th position of the isoxazole structure.

[0115] In the above reaction (q), a cyclic isoxazole structure is formed between the fluoroisobutylene derivative represented by general formula (11) and the amino group of the hydroxylamine represented by general formula (7). The -OR', -CF3, and -F groups of the fluoroisobutylene derivative are located at the 3-, 4-, and 5-positions of the formed isoxazole structure, respectively.

[0116] In the above reaction (r), a cyclic isoxazole structure is formed between the fluoroisobutane derivative represented by general formula (12) and the amino group of the hydroxylamine represented by general formula (7), and the compound represented by general formula (5) is then substituted onto the isoxazole structure. The -OR' and CF3 groups of the fluoroisobutane derivative are located at the 3rd and 4th positions, respectively, of the formed isoxazole structure, and X of the compound represented by general formula (5) is located at the 5th position of the isoxazole structure.

[0117] In the above reaction (s), a cyclic isoxazole structure is formed between the fluoroisobutane derivative represented by general formula (12) and the amino group of the hydroxylamine represented by general formula (7). The -OR', -CF3, and -F groups of the fluoroisobutane derivative are located at the 3-, 4-, and 5-positions of the formed isoxazole structure, respectively.

[0118] Hydrogen halide scavengers are substances that have the function of capturing the hydrogen fluoride (HF) that is produced. Examples of hydrogen halide scavengers include inorganic compounds such as sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, sodium fluoride, and potassium fluoride, organic nitrogen derivatives such as pyridine, triethylamine, diisopropylethylamine, diazabicyclononene, diazabicycloundecene, methyltriazabicyclodecene, and diazabicyclooctane, and phosphorus derivatives such as phosphazene bases.

[0119] Each of the above reactions (a) to (s) may be carried out in the presence of a fluoride ion scavenger, if necessary. The fluoride ion scavenger is preferably a salt of a cation of lithium, sodium, magnesium, potassium, calcium, or tetramethylammonium with an anion of trifluoroacetic acid, heptafluorobutyric acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, toluenesulfonic acid, trifluoromethanesulfonic acid, nonafluorobutanesulfonic acid, bis(trifluoromethanesulfonyl)imide, bis(nonafluorobutanesulfonyl)imide, N,N-hexafluoropropane-1,3-disulfonylimide, tetraphenylboric acid, tetrakis[3,5-bis(trifluoromethyl)phenyl]boric acid, or tetrakis(pentafluorophenyl)boric acid. Among these, potassium salts or sodium salts are preferred, and sodium salts are more preferred. It is believed that the cations derived from the fluoride ion scavenger capture fluorine ions liberated during the reaction and precipitate as a salt that has low solubility in organic solvents, thereby accelerating the reaction and enabling the production of a fluorinated isoxazole compound in high yield.

[0120] The reaction temperature in the above reactions (a) to (s) is preferably 0 to 100° C., more preferably 5 to 50° C., and even more preferably 10 to 20° C. The reaction time in the above reactions (a) to (s) is preferably 0.5 to 48 hours, more preferably 1 to 36 hours, and even more preferably 2 to 12 hours.

[0121] The solvent used in the above reactions (a) to (s) is preferably an organic solvent, such as aprotic polar solvents such as tetrahydrofuran, monoglyme, diglyme, triglyme, tetraglyme, acetonitrile, dimethylformamide, dimethylacetamide, methylpyrrolidone, 4-methyltetrahydropyran, dimethylethyleneurea, tetramethylurea, dimethyl sulfoxide, and sulfolane, or a two-phase solvent consisting of a protic polar solvent such as methanol or water and a non-aqueous solvent such as dichloromethane, toluene, and diethyl ether. Furthermore, as a catalyst for the above reactions (a) to (s), a quaternary ammonium halide such as benzyltriethylammonium chloride, a quaternary phosphonium halide, a crown ether, or the like can be optionally used.

[0122] Based on the above-described embodiments, the present invention relates to the following [1] to

[25] . [1] A fluorine-containing isoxazole compound represented by the following general formula (A): [ka] (In the above general formula (A), R represents a hydrogen atom or a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA 1 (OA 2 ), -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle, A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A 4 =C n H 2nrepresents an alkylene group represented by the formula: n is an integer from 1 to 20, Y 1 and Y 2 each independently represents N or O and is different from each other. [2] The fluorine-containing isoxazole compound according to the above item [1], which is a compound represented by the following general formula (1): [ka] (In the above general formula (1), X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA 1 (OA 2 ), -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle, A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20. [3] The fluorine-containing isoxazole compound according to the above item [1], which is a compound represented by the following general formula (2): [ka] (In the above general formula (2), R represents a substituted or unsubstituted hydrocarbon having 1 to 12 carbon atoms; X is a halogen atom, -OA 1 , -O-NA 1 A 2, -NA 1 A 2 , -NA 1 (OA 2 ), -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle, A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20. [4] The fluorine-containing isoxazole compound according to the above item [1], which is a compound represented by the following general formula (3): [ka] (In the above general formula (3), X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA 1 (OA 2 ), -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle, A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20. [5] The fluorine-containing isoxazole compound according to the above item [1], which is a compound represented by the following general formula (4): [ka] (In the above general formula (4), R' represents a substituted or unsubstituted hydrocarbon having 1 to 12 carbon atoms; X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA 1 (OA 2 ), -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle, A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20. [6] (I) A method of reacting a fluorine-containing compound selected from a fluorine-containing carbonyl compound, a fluoroisobutene derivative, and a fluoroisobutane derivative with hydroxylamine or a salt thereof, and optionally with a compound represented by the following general formula (5) or a salt thereof, or (II) A method for producing a compound represented by the general formula (5) or a salt thereof by reacting a fluorine-containing compound selected from the group consisting of a fluorine-containing carbonyl compound, a fluoroisobutene derivative, and a fluoroisobutane derivative with an amine salt or an amine compound, and optionally with the compound represented by the general formula (5) or a salt thereof: A method for producing a fluorinated isoxazole compound, comprising a step of synthesizing a fluorinated isoxazole compound represented by the following general formula (A): [ka] (In the above general formulas (A) and (5), R represents a hydrogen atom or a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA 1 (OA 2 ), -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle, A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20, Y 1 and Y 2 each independently represents N or O and is different from each other. [7] A method for producing a fluorine-containing isoxazole compound according to the above item [6], comprising a step of reacting a fluorine-containing carbonyl compound represented by the following general formula (6) with a hydroxylamine represented by the following general formula (7) or a salt thereof to obtain a fluorine-containing isoxazole compound represented by the following general formula (1): [ka] (In the above general formulas (1), (6) and (7), X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA 1 (OA 2 ), -NA 3-NA 1 A 2 , -NA 4 or a heterocycle, Z is -OA 5 , -O-NA 5 A 6 , -NA 5 A 6 , -NA 5 (OA 6 ), or -NA 7 -NA 5 A 6 represents A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20, A 5 , A 6 and A 7 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; The wavy bond indicates a single bond, representing either (E) or (Z) stereoisomerism.) [8] A method for producing a fluorine-containing isoxazole compound according to the above item [6], comprising a step of reacting a fluorine-containing carbonyl compound represented by the following general formula (8), a compound represented by the following general formula (5) or a salt thereof, and a hydroxylamine represented by the following general formula (7) or a salt thereof to obtain a fluorine-containing isoxazole compound represented by the following general formula (1): [ka] (In the above general formulas (1), (5) and (8), X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA 1 (OA2 ), -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle, Z is -OA 5 , -O-NA 6 A 7 , -NA 5 A 6 , -NA 5 (OA 6 ) or -NA 7 -NA 5 A 6 represents A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20, A 5 , A 6 and A 7 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms. [9] A method for producing a fluorine-containing isoxazole compound according to the above item [6], comprising the steps of reacting a fluorine-containing carbonyl compound represented by the following general formula (9) with a compound represented by the following general formula (5) or a salt thereof in the presence of a base, and then further reacting the resulting reaction product with a hydroxylamine represented by the following general formula (7) or a salt thereof to obtain a fluorine-containing isoxazole compound represented by the following general formula (1): [ka] (In the above general formulas (1), (5) and (9), X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA 1 (OA2 ), -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle, Z is -OA 5 , -O-NA 6 A 7 , -NA 5 A 6 , -NA 5 (OA 6 ) or -NA 7 -NA 5 A 6 represents A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20, A 5 , A 6 and A 7 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.

[10] A method for producing a fluorine-containing isoxazole compound according to the above item [6], comprising the steps of reacting a fluorine-containing carbonyl compound represented by the following general formula (10) with an alcohol, reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof in the presence of a base, and then reacting the resulting reaction product with hydroxylamine represented by the following general formula (7) or a salt thereof, thereby obtaining a fluorine-containing isoxazole compound represented by the following general formula (1): [ka] (In the above general formulas (1), (5) and (10), X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA1 (OA 2 ), -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle, A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20, W + represents an ammonium cation, an imidazolium cation, a pyridinium cation, a quinuclidium cation, or a phosphonium cation.

[11] A method for producing a fluorine-containing isoxazole compound according to the above item [6], comprising the steps of carbonylating a fluoroisobutene derivative represented by the following general formula (11) in the presence of a nucleophile, further reacting the derivative with an alcohol, reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof in the presence of a base, and then reacting the resulting reaction product with hydroxylamine represented by the following general formula (7) or a salt thereof, thereby obtaining a fluorine-containing isoxazole compound represented by the following general formula (1): [ka] (In the above general formulas (1), (5) and (11), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 (OA 2 ), -NA 1 A 2 , -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle, A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20.

[12] A method for producing a fluorine-containing isoxazole compound according to the above item [6], comprising the steps of: carbonylating a compound obtained by an elimination reaction of a fluoroisobutane derivative represented by the following general formula (12) in the presence of a nucleophile; further reacting the resulting reaction product with an alcohol; reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof in the presence of a base; and then reacting the resulting reaction product with hydroxylamine represented by the following general formula (7) or a salt thereof, thereby obtaining a fluorine-containing isoxazole compound represented by the following general formula (1). [ka] (In the above general formulas (1), (5) and (12), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA 1 (OA 2 ), -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle, Y is a halogen atom, -OB 1 , -SO m B 1 or -NB 1 B 2 represents m is an integer from 0 to 3, A 1 , A 2 and A 3each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20, B 1 and B 2 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.

[13] A method for producing a fluorine-containing isoxazole compound according to the above item [6], comprising a step of reacting a fluorine-containing carbonyl compound represented by the following general formula (13) with an amine salt or an amine compound to obtain a fluorine-containing isoxazole compound represented by the following general formula (2): [ka] (In the above general formulas (2) and (13), R represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X is -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA 1 (OA 2 ), -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle, A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20, The wavy bond indicates a single bond, representing either (E) or (Z) stereoisomerism.)

[14] A method for producing a fluorine-containing isoxazole compound according to the above item [6], comprising a step of reacting a fluorine-containing carbonyl compound represented by the following general formula (14), an amine salt or an amine compound, and optionally a compound represented by the following general formula (5) or a salt thereof, to obtain a fluorine-containing isoxazole compound represented by the following general formula (2): [ka] (In the above general formulas (2), (5) and (14), R represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 (OA 2 ), -NA 1 A 2 , -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle, A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20.

[15] A method for producing a fluorine-containing isoxazole compound according to the above item [6], comprising the steps of reacting a fluorine-containing carbonyl compound represented by the following general formula (15) with a compound represented by the following general formula (5) or a salt thereof in the presence of a base, and then reacting the resulting reaction product with an amine salt or an amine compound to obtain a fluorine-containing isoxazole compound represented by the following general formula (2): [ka] (In the above general formulas (2), (5) and (15), R represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA 1 (OA 2 ), -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle, A 1 , A 2 and A 3 each independently represents a hydrogen atom, a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, or a heterocycle; A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20.

[16] A method for producing a fluorine-containing isoxazole compound according to the above item [6], comprising the steps of reacting a fluorine-containing carbonyl compound represented by the following general formula (10) with an alcohol, reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof in the presence of a base, and then reacting the resulting reaction product with an amine salt or an amine compound to obtain a fluorine-containing isoxazole compound represented by the following general formula (2): [ka] (In the above general formulas (2), (5) and (10), R represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA 1 (OA 2 ), -NA 3 -NA 1 A 2 , -NA 4or a heterocycle, A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20, W + represents an ammonium cation, an imidazolium cation, a pyridinium cation, a quinuclidium cation, or a phosphonium cation.

[17] A method for producing a fluorine-containing isoxazole compound according to the above item [6], comprising the steps of carbonylating a fluoroisobutene derivative represented by the following general formula (11) in the presence of a nucleophile, further reacting the derivative with an alcohol, reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof in the presence of a base, and then reacting the resulting reaction product with an amine salt or an amine compound to obtain a fluorine-containing isoxazole compound represented by the following general formula (2): [ka] (In the above general formulas (2), (5) and (11), R and R' each independently represent a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA 1 (OA 2 ), -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle, A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20.

[18] A method for producing a fluorine-containing isoxazole compound according to the above item [6], comprising the steps of: carbonylating a compound obtained by an elimination reaction of a fluoroisobutane derivative represented by the following general formula (12) in the presence of a nucleophile; further reacting the resulting reaction product with an alcohol; reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof in the presence of a base; and then reacting the resulting reaction product with an amine salt or an amine compound, thereby obtaining a fluorine-containing isoxazole compound represented by the following general formula (2). [ka] (In the above general formulas (2), (5) and (12), R and R' each independently represent a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA 1 (OA 2 ), -NA 3 -NA 1 A 2 -NA 4 or a heterocycle, Y is a halogen atom, -OB 1 , -SO m B 1 or -NB 1 B 2 represents m is an integer from 0 to 3, A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; A 4 =C n H 2nrepresents an alkylene group represented by the formula: n is an integer from 1 to 20, B 1 and B 2 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.

[19] A method for producing a fluorine-containing isoxazole compound according to the above item [6], comprising the steps of reacting a fluorine-containing carbonyl compound represented by the following general formula (10) with a hydroxylamine represented by the following general formula (7) or a salt thereof, and further reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof, thereby obtaining a fluorine-containing isoxazole compound represented by the following general formula (3): [ka] (In the above general formulas (3), (5) and (10), X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA 1 (OA 2 ), -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle, A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20, W + represents an ammonium cation, an imidazolium cation, a pyridinium cation, a quinuclidium cation, or a phosphonium cation.

[20] A method for producing a fluorine-containing isoxazole compound according to the above item [6], comprising the steps of carbonylating a fluoroisobutene derivative represented by the following general formula (11) in the presence of a nucleophile, further reacting the fluoroisobutene derivative with a hydroxylamine represented by the following general formula (7) or a salt thereof, and then further reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof to obtain a fluorine-containing isoxazole compound represented by the following general formula (3): [ka] (In the above general formulas (3), (5) and (11), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA 1 (OA 2 ), -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle, A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20. [twenty one] A method for producing a fluorine-containing isoxazole compound according to the above item [6], comprising the steps of carbonylating a fluoroisobutane derivative represented by the following general formula (12) in the presence of a nucleophile, further reacting the derivative with a hydroxylamine represented by the following general formula (7) or a salt thereof, and then reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof to obtain a fluorine-containing isoxazole compound represented by the following general formula (3): [ka] (In the above general formulas (3), (5) and (12), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA 1 (OA 2 ), -NA 3 -NA 1 A 2 -NA 4 or a heterocycle, Y is a halogen atom, -OB 1 , -SO m B 1 or -NB 1 B 2 represents m is an integer from 0 to 3, A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20, B 1 and B 2 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms. [twenty two] A method for producing a fluorine-containing isoxazole compound according to the above item [6], comprising a step of reacting a fluoroisobutene derivative represented by the following general formula (11), a compound represented by the following general formula (5) or a salt thereof, and a hydroxylamine represented by the following general formula (7) or a salt thereof to obtain a fluorine-containing isoxazole compound represented by the following general formula (4): [ka] (In the above general formulas (4), (5) and (11), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 (OA 2 ), -NA 1 A 2 , -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle, A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20. [twenty three] A method for producing a fluorinated isoxazole compound according to the above item [6], comprising a step of reacting a fluoroisobutene derivative represented by the following general formula (11) with a hydroxylamine represented by the following general formula (7) or a salt thereof to obtain a fluorinated isoxazole compound represented by the following general formula (4-1): [ka] (In the above general formulas (4-1) and (11), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms. [twenty four] A method for producing a fluorine-containing isoxazole compound according to the above item [6], comprising a step of reacting a fluoroisobutane derivative represented by the following general formula (12), a compound represented by the following general formula (5) or a salt thereof, and a hydroxylamine represented by the following general formula (7) or a salt thereof to obtain a fluorine-containing isoxazole compound represented by the following general formula (4): [ka] (In the above general formulas (4), (5) and (12), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X is a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA 1 (OA 2 ), -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle, Y is a halogen atom, -OB 1 , -SO m B 1 or -NB 1 B 2 represents m is an integer from 0 to 3, A 1 , A 2 and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; A 4 =C n H 2n represents an alkylene group represented by the formula: n is an integer from 1 to 20, B 1 and B 2 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms. [twenty five] A method for producing a fluorine-containing isoxazole compound according to the above item [6], comprising a step of reacting a fluoroisobutane derivative represented by the following general formula (12) with a hydroxylamine represented by the following general formula (7) to obtain a fluorine-containing isoxazole compound represented by the following general formula (4-1): [ka] (In the above general formulas (4-1) and (12), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; Y is a halogen atom, -OB 1 , -SO m B 1 or -NB 1 B 2 represents m is an integer from 0 to 3, B 1 and B 2 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.

[0123] Although the embodiments of the present invention have been described above, the present invention is not limited to the above-described embodiments, but includes all aspects encompassed by the concept of the present invention and the scope of the claims, and can be modified in various ways within the scope of the present invention. [Example]

[0124] Examples of the present invention will be described below, but the present invention is not limited to these examples as long as they do not deviate from the spirit of the present invention. Note that the room temperature described below is in the range of 20°C ± 10°C.

[0125] Example 1 Preparation of 3-methoxy-4-(trifluoromethyl)-5-hydroxyisoxazole Under ice-water cooling, 1.0 g (14 mmol) of hydroxylamine hydrochloride was dissolved in 75 g of methanol. Subsequently, 5.7 g (56 mmol) of triethylamine was added dropwise so that the internal temperature did not exceed 10°C. Next, 2.7 g (14 mmol) of methyl 3,3-difluoro-2-(trifluoromethyl)acrylate was added dropwise so that the internal temperature did not exceed 10°C, and the mixture was heated to room temperature. After approximately 16 hours, 1N aqueous hydrochloric acid was added to adjust the pH of the reaction mixture to approximately 5, and ammonium chloride was added until saturated. The organic phase was dried over sodium sulfate, dissolved in a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate = 7:3), and purified using a silica gel column to obtain 0.2 g of the compound represented by the following formula (16). The isolation yield of the resulting compound was 8%.

[0126] [ka]

[0127] The analysis results were as follows: Mass spectrum (APCI, m / z): 183 ([M] + )

[0128] Example 2 Preparation of 3-ethoxy-4-(trifluoromethyl)-5-hydroxyisoxazole Under ice-water cooling, 1.0 g (14 mmol) of hydroxylamine hydrochloride was dissolved in 75 g of ethanol. Subsequently, 5.7 g (56 mmol) of triethylamine was added dropwise so that the internal temperature did not exceed 10°C. Next, 2.7 g (14 mmol) of methyl 3,3-difluoro-2-(trifluoromethyl)acrylate was added dropwise so that the internal temperature did not exceed 10°C, and the mixture was heated to room temperature. After approximately 16 hours, 1N aqueous hydrochloric acid was added to adjust the pH of the reaction mixture to approximately 5, and ammonium chloride was added until saturated. The organic phase was dried over sodium sulfate, dissolved in a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate = 7:3), and purified using a silica gel column to obtain 0.4 g of the compound represented by the following formula (17). The isolation yield of the resulting compound was 13%.

[0129] [ka]

[0130] The analysis results were as follows: Mass spectrum (APCI, m / z): 197 ([M] + )

[0131] Example 3 Preparation of 3-(dibenzylamino)-4-(trifluoromethyl)-5-hydroxyisoxazole Under ice-water cooling, 3.9 g (47 mmol) of 1-methylimidazole was added to 20 g of tetrahydrofuran. Subsequently, 10 g (47 mmol) of 1,3,3,3-tetrafluoro-1-methoxy-2-trifluoromethyl-1-propene was added dropwise so that the internal temperature did not exceed 10°C, and the mixture was allowed to warm to room temperature. After approximately 8 hours, a reaction mixture containing a salt of 3,3,3-trifluoro-2-(trifluoromethyl)propanoic acid fluoride anion and 1,3-dimethylimidazolium cation was obtained. Under ice-water cooling, this reaction mixture was added dropwise to a mixed solution of 5.6 g (47 mmol) of 2-(2-methoxyethoxy)ethanol and 20 g of tetrahydrofuran so that the internal temperature did not exceed 10°C, and the mixture was allowed to warm to room temperature. After approximately 8 hours, a reaction mixture containing 2-(2-methoxyethoxy)ethyl 3,3,3-trifluoro-2-(trifluoromethyl)propanoate was obtained. This reaction mixture was added dropwise to a mixed solution of 9.3 g (47 mmol) of dibenzylamine, 9.5 g (94 mmol) of triethylamine, and 20 g of tetrahydrofuran under ice-water cooling, so that the internal temperature did not exceed 10°C, and the mixture was allowed to warm to room temperature. After approximately 16 hours, a reaction mixture containing 2-(2-methoxyethoxy)ethyl (E / Z)-3-(dibenzylamino)-3-fluoro-2-(trifluoromethyl)acrylate was obtained. This reaction mixture was added dropwise to a mixed solution of 1.6 g (47 mmol) of hydroxylamine, 9.5 g (94 mmol) of triethylamine, and 20 g of tetrahydrofuran under ice-water cooling, so that the internal temperature did not exceed 10°C, and the mixture was allowed to warm to room temperature. After approximately 16 hours, 1 N aqueous hydrochloric acid was added to adjust the pH of the reaction mixture to approximately 5, and ammonium chloride was added until saturated. The organic phase was dried over sodium sulfate, dissolved in a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate=7:3), and purified using a silica gel column to obtain 0.5 g of the compound represented by the following formula (18). The isolated yield of the compound was 3%.

[0132] [ka]

[0133] The analysis results were as follows: Mass spectrum (APCI, m / z): 348 ([M] + )

[0134] Example 4 Preparation of 3-(dibenzylamino)-4-(trifluoromethyl)-5-hydroxyisoxazole using methyl 3,3,3-trifluoro-2-(trifluoromethyl)propanoate instead of 1,3,3,3-tetrafluoro-1-methoxy-2-trifluoromethyl-1-propene in Example 3 Under ice-water cooling, 1.9 g (9.5 mmol) of dibenzylamine and 1.9 g (19 mmol) of triethylamine were added to 30 g of tetrahydrofuran. Subsequently, 2.0 g (9.5 mmol) of methyl 3,3,3-trifluoro-2-(trifluoromethyl)propanoate was added dropwise so that the internal temperature did not exceed 10°C. After approximately 16 hours, a reaction mixture containing methyl (E / Z)-3-(dibenzylamino)-3-fluoro-2-(trifluoromethyl)acrylate was obtained. Under ice-water cooling, this reaction mixture was added dropwise to a mixed solution of 0.3 g (9.5 mmol) of hydroxylamine, 1.9 g (19 mmol) of triethylamine, and 30 g of tetrahydrofuran so that the internal temperature did not exceed 10°C, and the mixture was allowed to warm to room temperature. After approximately 16 hours, 1 N aqueous hydrochloric acid was added to adjust the pH of the reaction mixture to approximately 5, and ammonium chloride was added until saturated. The organic phase was dried over sodium sulfate, then dissolved in a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate=7:3) and purified using a silica gel column. The analytical results were the same as those of the product in Example 3.

[0135] Example 5 Preparation of 3-(1-azonanyl)-4-(trifluoromethyl)-5-hydroxyisoxazole Under ice-water cooling, 3.6 g (30 mmol) of 2-(2-methoxyethoxy)ethanol was added to 30 g of tetrahydrofuran. Subsequently, 10 g (30 mmol) of a salt of 3,3,3-trifluoro-2-(trifluoromethyl)propanoic acid fluoride anion and 1-methyl-4-dimethylaminopyridinium cation was added dropwise to a mixed solution of 30 g of tetrahydrofuran so that the internal temperature did not exceed 10°C, and the mixture was heated to room temperature. After approximately 8 hours, a reaction mixture containing 2-(2-methoxyethoxy)ethyl 3,3,3-trifluoro-2-(trifluoromethyl)propanoate was obtained. Under ice-water cooling, this reaction mixture was added dropwise to a mixed solution of 3.8 g (30 mmol) of azonan, 6.1 g (60 mmol) of triethylamine, and 30 g of tetrahydrofuran so that the internal temperature did not exceed 10°C, and the mixture was heated to room temperature. After approximately 16 hours, a reaction mixture containing 2-(2-methoxyethoxy)ethyl (E / Z)-3-(1-azonanyl)-3-fluoro-2-(trifluoromethyl)acrylate was obtained. This reaction mixture was added dropwise to a mixture of 1.0 g (30 mmol) of hydroxylamine, 6.1 g (60 mmol) of triethylamine, and 30 g of tetrahydrofuran under ice-water cooling, ensuring the internal temperature did not exceed 10°C. The mixture was then warmed to room temperature. After approximately 16 hours, 1N aqueous hydrochloric acid was added to adjust the pH of the reaction mixture to approximately 5, and ammonium chloride was added until saturated. The organic phase was dried over sodium sulfate, dissolved in a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate = 7:3), and purified using a silica gel column to obtain 0.9 g of the compound represented by formula (19). The isolated yield of the compound was 11%.

[0136] [ka]

[0137] The analysis results were as follows: Mass spectrum (APCI, m / z): 278 ([M] + )

[0138] Example 6 Preparation of 3-(1-azonanyl)-4-(trifluoromethyl)-5-hydroxyisoxazole using (E / Z)-3-(1-azonanyl)-3-fluoro-2-(trifluoromethyl)acrylate instead of the salt of 3,3,3-trifluoro-2-(trifluoromethyl)propanoic acid fluoride anion and 1-methyl-4-dimethylaminopyridinium cation in Example 5 Under ice-water cooling, 1.9 g (27 mmol) of hydroxylamine hydrochloride was dissolved in 60 g of methanol. Subsequently, 8.2 g (81 mmol) of triethylamine was added dropwise so that the internal temperature did not exceed 10°C. Next, 5 g (27 mmol) of methyl (E / Z)-3-(1-azonanyl)-3-fluoro-2-(trifluoromethyl)acrylate was added dropwise so that the internal temperature did not exceed 10°C, and the temperature was raised to room temperature. After approximately 16 hours, a 1N aqueous hydrochloric acid solution was added to adjust the pH of the reaction mixture to approximately 5, and ammonium chloride was added until saturated. The organic phase was dried over sodium sulfate, then dissolved in a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate = 7:3), and purified using a silica gel column. The analytical results were similar to those of the product in Example 5.

[0139] Example 7 Preparation of 3-(4,5,6,7-tetrahydrothieno[3,2-c]pyridin-5-yl)-4-(trifluoromethyl)-5-hydroxyisoxazole Under ice-water cooling, 20 g (86 mmol) of 1,1,1,3,3-pentafluoro-3-methoxy-2-trifluoromethyl-propane was added to 80 g of tetrahydrofuran. Subsequently, 11 g (86 mmol) of diisopropylethylamine was added dropwise so that the internal temperature did not exceed 10°C, and the mixture was heated to room temperature. After approximately 8 hours, a reaction mixture containing 1,3,3,3-tetrafluoro-1-methoxy-2-trifluoromethyl-1-propene was obtained. Under ice-water cooling, this reaction mixture was added dropwise to a mixed solution of 8.7 g (86 mmol) of triethylamine and 20 g of tetrahydrofuran so that the internal temperature did not exceed 10°C, and the mixture was heated to room temperature. After approximately 8 hours, a reaction mixture containing a salt of 3,3,3-trifluoro-2-(trifluoromethyl)propanoic acid fluoride anion and triethylmethylammonium cation was obtained. Under ice-water cooling, this reaction mixture was added to 10 g (86 mmol) of 2-(2-methoxyethoxy)ethanol and tetraethylmethylammonium cation. toThe mixture was added dropwise to a mixed solution of 20 g of tetrahydrofuran so that the internal temperature did not exceed 10°C, and the mixture was allowed to warm to room temperature. After approximately 8 hours, a reaction mixture containing 2-(2-methoxyethoxy)ethyl 3,3,3-trifluoro-2-(trifluoromethyl)propanoate was obtained. This reaction mixture was added dropwise to a mixed solution of 12 g (86 mmol) of 4,5,6,7-tetrahydrothieno[3,2-c]pyridine, 22 g (172 mmol) of diisopropylethylamine, and 40 g of tetrahydrofuran while cooling with ice water, so that the internal temperature did not exceed 10°C, and the mixture was allowed to warm to room temperature. After approximately 16 hours, a reaction mixture containing 2-(2-methoxyethoxy)ethyl (E / Z)-3-(4,5,6,7-tetrahydrothieno[3,2-c]pyridin-5-yl)-3-fluoro-2-(trifluoromethyl)acrylate was obtained. This reaction mixture was added dropwise to a mixed solution of 2.8 g (86 mmol) of hydroxylamine, 22 g (172 mmol) of diisopropylethylamine, and 30 g of tetrahydrofuran under ice-water cooling, ensuring that the internal temperature did not exceed 10°C, and the mixture was allowed to warm to room temperature. After approximately 16 hours, 1N aqueous hydrochloric acid was added to adjust the pH of the reaction mixture to approximately 5, and ammonium chloride was added until saturated. The organic phase was dried over sodium sulfate, then dissolved in a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate = 7:3), and purified using a silica gel column to obtain 0.5 g of the compound represented by the following formula (20). The isolated yield of the compound was 2%.

[0140] [ka]

[0141] The analysis results were as follows: Mass spectrum (APCI, m / z): 290 ([M] + )

[0142] Example 8 Preparation of 3-amino-N,N-dibenzyl-5-methoxy-4-(trifluoromethyl)isoxazole Under ice-water cooling, 1.1 g (3.0 mmol) of methyl 3-(dibenzylamino)-3-fluoro-2-(trifluoromethyl)-2-propenoate was added to 30 g of tetrahydrofuran, and 0.7 g (3.0 mmol) of 1-aminopyridinium iodide was dissolved therein. Subsequently, 0.8 g (6.0 mmol) of diisopropylethylamine was added dropwise so that the internal temperature did not exceed 10°C, and the mixture was heated to room temperature. After approximately 16 hours, the contents were dissolved in a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate = 7:3) and purified using a silica gel column to obtain 0.2 g of the compound represented by the following formula (21). The isolated yield of the resulting compound was 15%.

[0143] [ka]

[0144] The analysis results were as follows: Mass spectrum (APCI, m / z): 362 ([M] + ) 1 H-NMR (400MHz, CDCl3) δppm:7.33-7.24(m,10H), 4.65(s,4H), 3.86(s,3H)

[0145] Example 9 Preparation of 3-fluoro-5-methoxy-4-(trifluoromethyl)isoxazole Under ice-water cooling, 0.6 g (3.0 mmol) of methyl 3,3-difluoro-2-(trifluoromethyl)acrylate was added to 20 g of tetrahydrofuran. Subsequently, a solution of 0.9 g (3.0 mmol) of tetrabutylammonium azide in 20 g of tetrahydrofuran was added dropwise so that the internal temperature did not exceed 10°C, and the temperature was raised to room temperature. After approximately 72 hours, the contents were dissolved in a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate=7:3) and purified using a silica gel column to obtain 0.1 g of the compound represented by the following formula (22). The isolation yield of the obtained compound was 25%.

[0146] [ka]

[0147] The analysis results were as follows: Mass spectrum (APCI, m / z): 185 ([M] + )

[0148] Example 10 Preparation of 4-(3-(5-methoxy-4-(trifluoromethyl))isoxazolyl)thiomorpholine 1,1-dioxide Under ice-water cooling, 0.3 g (2.0 mmol) of thiomorpholine 1,1-dioxide and 0.5 g (4.0 mmol) of diisopropylethylamine were added to 20 g of tetrahydrofuran. Subsequently, 0.4 g (2.0 mmol) of methyl 3,3,3-trifluoro-2-(trifluoromethyl)propanoate was added dropwise so that the internal temperature did not exceed 10°C, and the mixture was allowed to warm to room temperature. After approximately 16 hours, the contents were cooled with ice-water, and 0.2 g (2.0 mmol) of hydroxylamine-O-sulfonic acid was added so that the internal temperature did not exceed 10°C. Subsequently, 0.8 g (6.0 mmol) of diisopropylethylamine was added dropwise, and the mixture was allowed to warm to room temperature. After approximately 36 hours, the contents were dissolved in a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate = 7:3) and purified using a silica gel column to obtain 0.1 g of the compound represented by the following formula (23). The isolation yield of the resulting compound was 9%.

[0149] [ka]

[0150] The analysis results were as follows: Mass spectrum (APCI, m / z): 300 ([M] + )

[0151] Example 11 Preparation of 5-ethoxy-3-((4-methoxybenzyl)oxy)-4-(trifluoromethyl)isoxazole Under ice-water cooling, 0.5 g (10.0 mmol) of ethanol was added to 20 g of tetrahydrofuran. Subsequently, a mixed solution of 3.0 g (9.0 mmol) of a salt of 3,3,3-trifluoro-2-(trifluoromethyl)propanoic acid fluoride anion and 1-methyl-4-dimethylaminopyridinium cation dissolved in 30 g of tetrahydrofuran was added dropwise so that the internal temperature did not exceed 10°C, and the mixture was heated to room temperature. After approximately 8 hours, the reaction mixture was cooled with ice-water, and a mixed solution of 1.2 g (9.0 mmol) of 4-methoxybenzyl alcohol, 1.8 g (18.0 mmol) of triethylamine, and 30 g of tetrahydrofuran was added dropwise so that the internal temperature did not exceed 10°C, and the mixture was heated to room temperature. After approximately 16 hours, the reaction mixture was cooled with ice water, and 2.6 g (9.0 mmol) of 1-aminopyridinium mesitylenesulfonate was added so that the internal temperature did not exceed 10°C. Subsequently, 2.3 g (18.0 mmol) of diisopropylethylamine was added dropwise, and the temperature was raised to room temperature. After approximately 16 hours, the contents were dissolved in a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate=7:3) and purified using a silica gel column to obtain 0.2 g of the compound represented by the following formula (24). The isolated yield of the compound was 8%.

[0152] [ka]

[0153] The analysis results were as follows: Mass spectrum (APCI, m / z): 317 ([M] + )

[0154] Example 12 Preparation of 3-amino-5-((2-ethylhexyl)oxy)-N-methyl-N-(3-pyridyl)-4-(trifluoromethyl)isoxazole Under ice-water cooling, 3.9 g (47.0 mmol) of 1-methylimidazole was added to 20 g of tetrahydrofuran. Subsequently, 10 g (47.0 mmol) of 1,3,3,3-tetrafluoro-1-methoxy-2-trifluoromethyl-1-propene was added dropwise so that the internal temperature did not exceed 10°C, and the mixture was allowed to warm to room temperature. After approximately 8 hours, a reaction mixture containing a salt of 3,3,3-trifluoro-2-(trifluoromethyl)propanoic acid fluoride anion and 1,3-dimethylimidazolium cation was obtained. Under ice-water cooling, this reaction mixture was added dropwise to a mixed solution of 6.1 g (47.0 mmol) of 2-ethyl-1-hexanol and 20 g of tetrahydrofuran so that the internal temperature did not exceed 10°C, and the mixture was allowed to warm to room temperature. After approximately 8 hours, a reaction mixture containing 2-ethylhexyl 3,3,3-trifluoro-2-(trifluoromethyl)propanoate was obtained. This reaction mixture was added dropwise to a mixture of 5.1 g (47.0 mmol) of 3-(methylamino)pyridine, 9.5 g (94.0 mmol) of triethylamine, and 20 g of tetrahydrofuran under ice-water cooling, ensuring that the internal temperature did not exceed 10°C, and the mixture was allowed to warm to room temperature. After approximately 16 hours, this reaction mixture was added dropwise to a mixture of 10 g (47.0 mmol) of o-(mesitylenesulfonyl)hydroxylamine, 9.5 g (94.0 mmol) of triethylamine, and 20 g of tetrahydrofuran under ice-water cooling, ensuring that the internal temperature did not exceed 10°C, and the mixture was allowed to warm to room temperature. After approximately 16 hours, 1N aqueous hydrochloric acid was added to the reaction mixture to adjust the pH to approximately 5, and ammonium chloride was added until saturated. The organic phase was dried over sodium sulfate, dissolved in a mixture of hexane and ethyl acetate (hexane:ethyl acetate = 7:3), and purified using a silica gel column to obtain 0.5 g of the compound represented by formula (25): The isolated yield of the obtained compound was 3%.

[0155] [ka]

[0156] The analysis results were as follows: Mass spectrum (APCI, m / z): 371 ([M] + )

[0157] Example 13 Preparation of 4-(3-(5-(2-methoxy)ethoxy-4-(trifluoromethyl))isoxazolyl)-2-piperazinone Under ice-water cooling, 20 g (86.0 mmol) of 1,1,1,3,3-pentafluoro-3-methoxy-2-trifluoromethyl-propane was added to 80 g of tetrahydrofuran. Subsequently, 11 g (86.0 mmol) of diisopropylethylamine was added dropwise so that the internal temperature did not exceed 10°C, and the mixture was heated to room temperature. After approximately 8 hours, a reaction mixture containing 1,3,3,3-tetrafluoro-1-methoxy-2-trifluoromethyl-1-propene was obtained. Under ice-water cooling, this reaction mixture was added dropwise to a mixed solution of 9.6 g (86.0 mmol) of quinuclidine and 20 g of tetrahydrofuran so that the internal temperature did not exceed 10°C, and the mixture was heated to room temperature. After approximately 8 hours, a reaction mixture containing a salt of 3,3,3-trifluoro-2-(trifluoromethyl)propanoic acid fluoride anion and N-methylquinuclidinium cation was obtained. This reaction mixture was added dropwise to a mixed solution of 6.5 g (86.0 mmol) of 2-methoxyethanol and 20 g of tetrahydrofuran under ice-water cooling so that the internal temperature did not exceed 10°C, and the mixture was then warmed to room temperature. After approximately 8 hours, a reaction mixture containing 2-methoxyethyl 3,3,3-trifluoro-2-(trifluoromethyl)propanoate was obtained. This reaction mixture was added dropwise to a mixed solution of 8.6 g (86.0 mmol) of piperazinone, 22 g (172.0 mmol) of diisopropylethylamine, and 40 g of tetrahydrofuran under ice-water cooling so that the internal temperature did not exceed 10°C, and the mixture was then warmed to room temperature. After approximately 16 hours, this reaction mixture was added dropwise to a mixture of 16 g (86.0 mmol) of 1,1,1-trimethylhydrazinium trifluoroacetate, 22 g (172.0 mmol) of diisopropylethylamine, and 30 g of tetrahydrofuran under ice-water cooling, ensuring that the internal temperature did not exceed 10°C, and the mixture was allowed to warm to room temperature. After approximately 16 hours, 1N aqueous hydrochloric acid was added to adjust the pH of the reaction mixture to approximately 5, and ammonium chloride was added until saturated. The organic phase was dried over sodium sulfate, dissolved in a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate = 7:3), and purified using a silica gel column to obtain 0.5 g of the compound represented by the following formula (26). The isolated yield of the compound was 2%.

[0158] [ka]

[0159] The analysis results were as follows: Mass spectrum (APCI, m / z): 309 ([M] + )

[0160] Example 14 Preparation of 5-(1H-benzo[d][1,2,3]triazol-1-yl)-4-(trifluoromethyl)isoxazol-3-ol Under ice-water cooling, 2 g (6.4 mmol) of hydroxylammonium bistrifluoromethanesulfonylimide was dissolved in 30 g of tetrahydrofuran. Subsequently, a mixed solution of 1.9 g (6.4 mmol) of 3,3,3-trifluoro-2-(trifluoromethyl)propanoic acid fluoride anion and N-methylimidazolium cation dissolved in 20 g of tetrahydrofuran was added dropwise so that the internal temperature did not exceed 10 °C, and the mixture was allowed to warm to room temperature. After approximately 3 hours, the reaction mixture was cooled with ice-water, and 0.7 g (6.4 mmol) of triethylamine was added dropwise so that the internal temperature did not exceed 10 °C, and the mixture was allowed to warm to room temperature. After approximately 4 hours, the reaction mixture was cooled with ice-water, and a mixed solution of 0.8 g (6.4 mmol) of 1,2,3-benzotriazole, 2.3 g (23.0 mmol) of triethylamine, and 30 g of tetrahydrofuran was added dropwise so that the internal temperature did not exceed 10 °C, and the mixture was allowed to warm to room temperature. After about 16 hours, the contents were dissolved in a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate=7:3) and purified using a silica gel column to obtain 0.3 g of the compound represented by the following formula (27). The isolated yield of the obtained compound was 17%.

[0161] [ka]

[0162] The analysis results were as follows: Mass spectrum (APCI, m / z): 270 ([M] + ) 1H-NMR (400MHz, CDCl3) δppm:8.19(dd,1H), 8.12(dd,1H), 7.41(ddd,1H), 7.33(ddd,1H)

[0163] Example 15 Preparation of 5-(10H-spiro[acridine-9,9'-fluoren]-10-yl)-4-(trifluoromethyl)isoxazol-3-ol Under ice-water cooling, 0.9 g (8.5 mmol) of triethylamine was added to 20 g of acetonitrile. Subsequently, 1.8 g (8.5 mmol) of 1,3,3,3-tetrafluoro-1-methoxy-2-trifluoromethyl-1-propene was added dropwise so that the internal temperature did not exceed 10°C, and the mixture was heated to room temperature. After approximately 4 hours, under ice-water cooling, the reaction mixture was added dropwise to a mixed solution of 3.0 g (8.5 mmol) of hydroxylammonium tetraphenylborate and 20 g of acetonitrile so that the internal temperature did not exceed 10°C, and the mixture was heated to room temperature. After approximately 3 hours, the reaction mixture was cooled with ice-water, and 0.9 g (8.5 mmol) of triethylamine was added dropwise so that the internal temperature did not exceed 10°C, and the mixture was heated to room temperature. After approximately 4 hours, the reaction mixture was added dropwise to a mixture of 2.8 g (8.5 mmol) of 10H-spiro[acridine-9,9'-fluorene], 3.0 g (30.0 mmol) of triethylamine, and 20 g of acetonitrile under ice-water cooling, ensuring that the internal temperature did not exceed 10°C, and the mixture was allowed to warm to room temperature. After approximately 16 hours, the contents were dissolved in a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate = 7:3) and purified using a silica gel column to obtain 0.4 g of the compound represented by the following formula (27). The isolated yield of the compound was 10%.

[0164] [ka]

[0165] The analysis results were as follows: Mass spectrum (APCI, m / z): 482 ([M] + )

[0166] Example 16 Preparation of 5-((2,2,4,4-tetramethylpentan-3-ylidene)amino)-4-(trifluoromethyl)isoxazol-3-ol Under ice-water cooling, 1.1 g (4.8 mmol) of 1,1,1,3,3-pentafluoro-3-methoxy-2-trifluoromethyl-propane was added to 40 g of tetrahydrofuran. Subsequently, 0.6 g (4.8 mmol) of diisopropylethylamine was added dropwise so that the internal temperature did not exceed 10°C, and the mixture was warmed to room temperature. After approximately 4 hours, under ice-water cooling, the reaction mixture was added dropwise to a mixed solution of 0.6 g (4.8 mmol) of 4-dimethylaminopyridine and 15 g of tetrahydrofuran so that the internal temperature did not exceed 10°C, and the mixture was warmed to room temperature. After approximately 4 hours, under ice-water cooling, the reaction mixture was added dropwise to a mixed solution of 1.5 g (4.8 mmol) of hydroxylammonium bistrifluoromethanesulfonylimide and 20 g of tetrahydrofuran so that the internal temperature did not exceed 10°C, and the mixture was warmed to room temperature. After approximately 3 hours, the reaction mixture was cooled with ice water, and 0.6 g (4.8 mmol) of diisopropylethylamine was added dropwise so that the internal temperature did not exceed 10°C. The mixture was then warmed to room temperature. After approximately 4 hours, the reaction mixture was added dropwise to a mixture of 0.7 g (4.8 mmol) of 2,2,4,4-tetramethyl-3-pentanoneimine, 2.8 g (22.0 mmol) of diisopropylethylamine, and 20 g of tetrahydrofuran while cooling with ice water, so that the internal temperature did not exceed 10°C. The mixture was then warmed to room temperature. After approximately 16 hours, the contents were dissolved in a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate = 7:3) and purified with a silica gel column to obtain 0.1 g of the compound represented by the following formula (28). The isolated yield of the compound was 9%.

[0167] [ka]

[0168] The analysis results were as follows: Mass spectrum (APCI, m / z): 292 ([M] + )

[0169] Example 17 Preparation of 5-fluoro-3-methoxy-4-trifluoromethylisoxazole Under ice-water cooling, 3.1 g (10.0 mmol) of hydroxylammonium bis(trifluoromethylsulfonyl)amine and 2.1 g (10.0 mmol) of 1,3,3,3-tetrafluoro-1-methoxy-2-trifluoromethyl-1-propene were added to 75 g of 4-methyltetrahydropyran. Subsequently, a solution of 4.7 g (20.0 mmol) of tert-butylimino-tris(dimethylamino)phosphorane in 25 g of 4-methyltetrahydropyran was added dropwise so that the internal temperature did not exceed 10 °C, and the temperature was raised to room temperature. After approximately 16 hours, the mixture was cooled with ice-water, and a solution of 6.1 g (26.0 mmol) of tert-butylimino-tris(dimethylamino)phosphorane in 20 g of 4-methyltetrahydropyran was added dropwise so that the internal temperature did not exceed 10 °C, and the temperature was raised to room temperature. After about 8 hours, the reaction mixture was dissolved in a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate=7:3) and purified using a silica gel column to obtain 0.04 g of the compound represented by the following formula (29). The isolated yield of the obtained compound was 2%.

[0170] [ka]

[0171] The analysis results were as follows: Mass spectrum (APCI, m / z): 185 ([M] + )

[0172] Example 18 Preparation of 3-methoxy-5-morpholinyl-4-trifluoromethylisoxazole Under ice-water cooling, 0.7 g (10.0 mmol) of hydroxylamine hydrochloride and 2.1 g (10.0 mmol) of 1,3,3,3-tetrafluoro-1-methoxy-2-trifluoromethyl-1-propene were added to 30 g of methanol. Subsequently, a solution of 2.0 g (20.0 mmol) of triethylamine in 10 g of methanol was added dropwise so that the internal temperature did not exceed 10°C, and the mixture was allowed to warm to room temperature. After approximately 16 hours, the mixture was cooled with ice-water, and a solution of 4.5 g (52.0 mmol) of morpholine in 15 g of methanol was added dropwise so that the internal temperature did not exceed 10°C, and the mixture was allowed to warm to room temperature. After approximately 8 hours, the reaction mixture was dissolved in a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate = 7:3) and purified using a silica gel column to obtain 0.5 g of the compound represented by the following formula (30). The isolated yield of the resulting compound was 18%.

[0173] [ka]

[0174] The analysis results were as follows: Mass spectrum (APCI, m / z): 252 ([M] + ) 1 H-NMR (400MHz, CDCl3) δppm:3.80(m,7H), 3.50(dd,4H)

[0175] Example 19 Preparation of 5-fluoro-3-methoxy-4-trifluoromethylisoxazole using 1,1,1,3,3-pentafluoro-3-methoxy-2-trifluoromethyl-propane instead of 1,3,3,3-tetrafluoro-1-methoxy-2-trifluoromethyl-1-propene in Example 17 Under ice-water cooling, 3.1 g (10 mmol) of hydroxylammonium bis(trifluoromethylsulfonyl)amine and 23 g (10 mmol) of 1,1,1,3,3-pentafluoro-3-methoxy-2-trifluoromethyl-propane were added to 75 g of 4-methyltetrahydropyran. Subsequently, a solution of 7.1 g (30 mmol) of tert-butylimino-tris(dimethylamino)phosphorane in 25 g of 4-methyltetrahydropyran was added dropwise so that the internal temperature did not exceed 10°C, and the mixture was allowed to warm to room temperature. After approximately 16 hours, the mixture was cooled with ice-water, and a solution of 6.1 g (26 mmol) of tert-butylimino-tris(dimethylamino)phosphorane in 20 g of 4-methyltetrahydropyran was added dropwise so that the internal temperature did not exceed 10°C, and the mixture was allowed to warm to room temperature. After about 8 hours, the reaction mixture was dissolved in a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate=7:3) and purified using a silica gel column. The analytical results of the obtained compound were the same as those of the product in Example 17.

[0176] In addition, in Example 19, the isolation yield of the obtained compound is not calculated, but due to the by-products that may be generated in the process of generating 1,3,3,3-tetrafluoro-1-methoxy-2-(trifluoromethyl)-1-propene from 1,1,1,3,3-pentafluoro-3-methoxy-2-(trifluoromethyl)-propane in the system, the types of impurities and their amount are expected to increase.Therefore, it is considered that the isolation yield of the obtained product is higher in the preparation method of Example 17 than in the preparation method of corresponding Example 19.

[0177] Example 20 Preparation of 5-(1-benzimidazolyl)-3-methoxy-4-trifluoromethylisoxazole Under ice-water cooling, 1.0 g (14 mmol) of hydroxylamine hydrochloride and 3.1 g (14 mmol) of 1,3,3,3-tetrafluoro-1-methoxy-2-trifluoromethyl-1-propene were added to 45 g of methanol. Subsequently, a solution of 2.9 g (28 mmol) of triethylamine in 20 g of methanol was added dropwise so that the internal temperature did not exceed 10°C, and the mixture was allowed to warm to room temperature. After approximately 16 hours, the mixture was cooled with ice-water, and a solution of 1.7 g (14 mmol) of benzimidazole and 4.4 g (42 mmol) of triethylamine in 20 g of methanol was added dropwise so that the internal temperature did not exceed 10°C, and the mixture was allowed to warm to room temperature. After approximately 8 hours, the reaction mixture was dissolved in a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate = 7:3) and purified using a silica gel column to obtain 0.6 g of the compound represented by formula (31). The isolated yield of the resulting compound was 15%.

[0178] [ka]

[0179] The analysis results were as follows: Mass spectrum (APCI, m / z): 283 ([M] + ) 1 H-NMR (400MHz, CDCl3) δppm:8.21(s,1H), 7.90(d,1H), 7.70(d,1H), 7.46(dd,2H), 4.16(m,3H)

[0180] Example 21 Preparation of 3-methoxy-5-(N-methoxymethylamino)-4-trifluoromethylisoxazole Under ice-water cooling, 1.0 g (14 mmol) of hydroxylamine hydrochloride and 3.1 g (14 mmol) of 1,3,3,3-tetrafluoro-1-methoxy-2-trifluoromethyl-1-propene were added to 45 g of methanol. Subsequently, a solution of 2.9 g (28 mmol) of triethylamine in 20 g of methanol was added dropwise so that the internal temperature did not exceed 10°C, and the mixture was allowed to warm to room temperature. After approximately 16 hours, the mixture was cooled with ice-water, and a solution of 1.4 g (14 mmol) of N-methoxymethylamine hydrochloride and 5.8 g (56 mmol) of triethylamine in 20 g of methanol was added dropwise so that the internal temperature did not exceed 10°C, and the mixture was allowed to warm to room temperature. After approximately 8 hours, the reaction mixture was dissolved in a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate = 7:3) and purified using a silica gel column to obtain 0.3 g of the compound represented by formula (32). The isolated yield of the resulting compound was 8%.

[0181] [ka]

[0182] The analysis results were as follows: Mass spectrum (APCI, m / z): 226 ([M] + ) 1 H-NMR (400MHz, CDCl3) δppm:3.98(s,3H), 3.74(s,3H), 3.21(s,3H)

[0183] Example 22 Preparation of 5-[(N-diphenylmethylene)amino]-3-methoxy-4-trifluoromethylisoxazole To 14 ml of methanol were added 0.5 g (7.3 mmol) of hydroxylamine hydrochloride and 1.5 g (7.1 mmol) of 1,3,3,3-tetrafluoro-1-methoxy-2-trifluoromethyl-1-propene. After cooling to 0°C, 1.5 g (14.6 mmol) of triethylamine was added dropwise and the mixture was warmed to room temperature. After approximately 19 hours, the mixture was cooled to 0°C, and 1.3 g (7.2 mmol) of benzophenone imine and 2.2 g (21.8 mmol) of triethylamine were added dropwise, followed by heating to 60°C. After approximately 7 hours, the mixture was cooled and purified using a silica gel column to obtain a trace amount of the compound represented by formula (33).

[0184] [ka]

[0185] The analysis results were as follows: Mass spectrum (APCI, m / z): 346 ([M] + )

Claims

1. A fluorine-containing isoxazole compound represented by the following general formula (A): 【Chemistry 1】 (In the above general formula (A), R represents a hydrogen atom or a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X is a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA ３ -NA １ A ２ , -NA ４ or a heterocycle, A １ , A ２ and A ３ each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A ４ Is = C ｎ H ２ｎ represents an alkylene group represented by the formula: n is an integer from 1 to 20, Y １ and Y ２ each independently represents N or O and is different from each other.

2. 2. The fluorine-containing isoxazole compound according to claim 1, which is a compound represented by the following general formula (1), (2), (3) or (4): 【Chemistry 2】 (In the above general formula (1), X is a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA ３ -NA １ A ２ , -NA ４ or a heterocycle, A １ , A ２ and A ３ each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A ４ Is = C ｎ H ２ｎ represents an alkylene group represented by the formula: n is an integer from 1 to 20; 【Transformation 3】 (In the above general formula (2), R represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X is a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA ３ -NA １ A ２ , -NA ４ or a heterocycle, A １ , A ２ and A ３ each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A ４ Is = C ｎ H ２ｎ represents an alkylene group represented by the formula: n is an integer from 1 to 20; 【Chemistry 4】 (In the above general formula (3), X is a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA ３ -NA １ A ２ , -NA ４ or a heterocycle, A １ , A ２ and A ３ each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A ４ Is = C ｎ H ２ｎ represents an alkylene group represented by the formula: n is an integer from 1 to 20; or 【Transformation 5】 (In the above general formula (4), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X is a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA ３ -NA １ A ２ , -NA ４ or a heterocycle, A １ , A ２ and A ３ each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A ４ Is = C ｎ H ２ｎ represents an alkylene group represented by the formula: n is an integer from 1 to 20.

3. The method includes a step of reacting a fluorine-containing compound selected from a fluorine-containing carbonyl compound, a fluoroisobutene derivative, and a fluoroisobutane derivative with hydroxylamine or a salt thereof, and optionally with a compound represented by the following general formula (5) or a salt thereof, to synthesize a fluorine-containing isoxazole compound represented by the following general formula (A): The method for producing a fluorine-containing isoxazole compound, wherein the fluorine-containing carbonyl compound, the fluoroisobutene derivative, and the fluoroisobutane derivative have any one structure selected from the group consisting of the following general formulas (6), and (8) to (15): 【Transformation 6】 (In the above general formulas (A) and (5), R represents a hydrogen atom or a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X is a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA ３ -NA １ A ２ , -NA ４ or a heterocycle, A １ , A ２ and A ３ each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A ４ Is = C ｎ H ２ｎ represents an alkylene group represented by the formula: n is an integer from 1 to 20, Y １ and Y ２ each independently represents N or O and is different from each other. 【Transformation 7】 (In the above general formulas (6), (8) to (15), R and R' each represent a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X represents a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA 1 (OA 2 ), -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle; Y represents a halogen atom, —OB 1 , —SO m B 1 or —NB 1 B 2 ; m is an integer from 0 to 3; Z represents -OA 5 , -O-NA 5 A 6 , -NA 5 A 6 , -NA 5 (OA 6 ), or -NA 7 -NA 5 A 6 ; A 1 , A 2 and A 3 each independently represent a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A 4 represents an alkylene group represented by ═C n H 2n ; n is an integer from 1 to 20, A 5 , A 6 and A 7 each independently represent a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; B 1 and B 2 each independently represent a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; W + represents an ammonium cation, an imidazolium cation, a pyridinium cation, a quinuclidium cation, or a phosphonium cation; The wavy bond indicates a single bond representing either (E) or (Z) stereoisomerism.

4. A method for producing a fluorine-containing isoxazole compound represented by the following general formula (A) by reacting a fluorine-containing compound selected from a fluorine-containing carbonyl compound, a fluoroisobutene derivative, and a fluoroisobutane derivative with an amine salt or an amine compound, and optionally with a compound represented by the following general formula (5) or a salt thereof: The fluorine-containing carbonyl compound, the fluoroisobutene derivative, and the fluoroisobutane derivative have any one structure selected from the group consisting of the following general formulas (6), (8) to (15): The amine salt or amine compound is an amine salt of a nitrogen-containing heterocyclic cation in which one amino group (-NH 2 ) is bonded to a nitrogen atom in the heterocycle or a quaternary ammonium cation in which one amino group (-NH 2 ) is bonded to a nitrogen atom, with an anion selected from halogen, sulfuric acid, phosphoric acid, sulfonic acid, trifluoroacetic acid, tetrafluoroborate, tetraphenylborate, hexafluoroborate, and sulfonylimide acid; a primary amine, hydroxylamine, or amine salt having an anionic substituent or anion selected from halogen, sulfuric acid, phosphoric acid, sulfonic acid, and trifluoroacetic acid; or a quaternary ammonium salt substituted with a hydrocarbon group selected from alkyl and aryl groups. 【Transformation 8】 (In the above general formulas (A) and (5), R represents a hydrogen atom or a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X represents a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA 1 (OA 2 ), -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle; A 1 , A 2 and A 3 each independently represent a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A 4 represents an alkylene group represented by ═C n H 2n ; n is an integer from 1 to 20, Y 1 and Y 2 each independently represent N or O and are different from each other. 【Chemistry 9】 (In the above general formulas (6), (8) to (15), R and R' each represent a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X represents a halogen atom, -OA 1 , -O-NA 1 A 2 , -NA 1 A 2 , -NA 1 (OA 2 ), -NA 3 -NA 1 A 2 , -NA 4 or a heterocycle; Y represents a halogen atom, —OB 1 , —SO m B 1 or —NB 1 B 2 ; m is an integer from 0 to 3; Z represents -OA 5 , -O-NA 5 A 6 , -NA 5 A 6 , -NA 5 (OA 6 ), or -NA 7 -NA 5 A 6 ; A 1 , A 2 and A 3 each independently represent a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A 4 represents an alkylene group represented by ═C n H 2n ; n is an integer from 1 to 20, A 5 , A 6 and A 7 each independently represent a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; B 1 and B 2 each independently represent a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; W + represents an ammonium cation, an imidazolium cation, a pyridinium cation, a quinuclidium cation, or a phosphonium cation; The wavy bond indicates a single bond representing either (E) or (Z) stereoisomerism.

5. 4. A method for producing a fluorine-containing isoxazole compound according to claim 3, comprising a step of reacting a fluorine-containing carbonyl compound represented by the following general formula (6) with a hydroxylamine represented by the following general formula (7) or a salt thereof to obtain a fluorine-containing isoxazole compound represented by the following general formula (1): 【Chemistry 10】 (In the above general formulas (1), (6) and (7), X is a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, Z is -OA ５ , -O-NA ５ A ６ , -NA ５ A ６ , -NA ５ (OA ６ ), or -NA ７ -NA ５ A ６ represents A １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A ４ Is = C ｎ H ２ｎ represents an alkylene group represented by the formula: n is an integer from 1 to 20, A ５ , A ６ and A ７ each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; The wavy bond indicates a single bond representing either (E) or (Z) stereoisomerism.

6. 4. A method for producing a fluorine-containing isoxazole compound according to claim 3, comprising a step of reacting a fluorine-containing carbonyl compound represented by the following general formula (8), a compound represented by the following general formula (5) or a salt thereof, and a hydroxylamine represented by the following general formula (7) or a salt thereof to obtain a fluorine-containing isoxazole compound represented by the following general formula (1): 【Chemistry 11】 (In the above general formulas (1), (5) and (8), X is a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, Z is -OA ５ , -O-NA ６ A ７ , -NA ５ A ６ , -NA ５ (OA ６ ) or -NA ７ -NA ５ A ６ represents A １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A ４ Is = C ｎ H ２ｎ represents an alkylene group represented by the formula: n is an integer from 1 to 20, A ５ , A ６ and A ７ each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.

7. 4. A method for producing a fluorine-containing isoxazole compound according to claim 3, comprising the steps of reacting a fluorine-containing carbonyl compound represented by the following general formula (9) with a compound represented by the following general formula (5) or a salt thereof in the presence of a base, and then further reacting the obtained reaction product with a hydroxylamine represented by the following general formula (7) or a salt thereof to obtain a fluorine-containing isoxazole compound represented by the following general formula (1): 【Chemistry 12】 (In the above general formulas (1), (5) and (9), X is a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, Z is -OA ５ , -O-NA ６ A ７ , -NA ５ A ６ , -NA ５ (OA ６ ) or -NA ７ -NA ５ A ６ represents A １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A ４ Is = C ｎ H ２ｎ represents an alkylene group represented by the formula: n is an integer from 1 to 20, A ５ , A ６ and A ７ each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.

8. 4. A method for producing a fluorine-containing isoxazole compound according to claim 3, comprising the steps of reacting a fluorine-containing carbonyl compound represented by the following general formula (10) with an alcohol, reacting the obtained reaction product with a compound represented by the following general formula (5) or a salt thereof in the presence of a base, and then reacting the resulting reaction product with hydroxylamine represented by the following general formula (7) or a salt thereof, thereby obtaining a fluorine-containing isoxazole compound represented by the following general formula (1): 【Chemistry 13】 (In the above general formulas (1), (5) and (10), X is a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, A １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A ４ Is = C ｎ H ２ｎ represents an alkylene group represented by the formula: n is an integer from 1 to 20, W ＋ represents an ammonium cation, an imidazolium cation, a pyridinium cation, a quinuclidium cation, or a phosphonium cation.

9. 4. A method for producing a fluorine-containing isoxazole compound according to claim 3, comprising the steps of: carbonylating a fluoroisobutene derivative represented by the following general formula (11) in the presence of a nucleophile, further reacting the resulting reaction product with an alcohol, reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof in the presence of a base, and then reacting the resulting reaction product with hydroxylamine represented by the following general formula (7) or a salt thereof, thereby obtaining a fluorine-containing isoxazole compound represented by the following general formula (1): 【Chemistry 14】 (In the above general formulas (1), (5) and (11), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X is a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ (OA ２ ), -NA １ A ２ , -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, A １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; A ４ Is = C ｎ H ２ｎ represents an alkylene group represented by the formula: n is an integer from 1 to 20.

10. 4. A method for producing a fluorine-containing isoxazole compound according to claim 3, comprising the steps of: carbonylating a compound obtained by an elimination reaction of a fluoroisobutane derivative represented by the following general formula (12) in the presence of a nucleophile; further reacting the resulting reaction product with an alcohol; reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof in the presence of a base; and then reacting the resulting reaction product with hydroxylamine represented by the following general formula (7) or a salt thereof, thereby obtaining a fluorine-containing isoxazole compound represented by the following general formula (1): 【Chemistry 15】 (In the above general formulas (1), (5) and (12), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X is a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, Y is a halogen atom, —OB １ , -SO ｍ B １ or -NB １ B ２ represents m is an integer from 0 to 3; A １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; A ４ Is = C ｎ H ２ｎ represents an alkylene group represented by the formula: n is an integer from 1 to 20, B １ and B ２ each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.

11. 5. A method for producing a fluorine-containing isoxazole compound according to claim 4, comprising a step of reacting a fluorine-containing carbonyl compound represented by the following general formula (13) with an amine salt or an amine compound to obtain a fluorine-containing isoxazole compound represented by the following general formula (2): 【Chemistry 16】 (In the above general formulas (2) and (13), R represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X is -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, A １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A ４ Is = C ｎ H ２ｎ represents an alkylene group represented by the formula: n is an integer from 1 to 20, The wavy bond indicates a single bond representing either (E) or (Z) stereoisomerism.

12. 5. A method for producing a fluorine-containing isoxazole compound according to claim 4, comprising a step of reacting a fluorine-containing carbonyl compound represented by the following general formula (14), an amine salt or an amine compound, and optionally a compound represented by the following general formula (5) or a salt thereof, to obtain a fluorine-containing isoxazole compound represented by the following general formula (2): 【Chemistry 17】 (In the above general formulas (2), (5) and (14), R represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X is a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ (OA ２ ), -NA １ A ２ , -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, A １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; A ４ Is = C ｎ H ２ｎ represents an alkylene group represented by the formula: n is an integer from 1 to 20.

13. 5. A method for producing a fluorine-containing isoxazole compound according to claim 4, comprising the steps of reacting a fluorine-containing carbonyl compound represented by the following general formula (15) with a compound represented by the following general formula (5) or a salt thereof in the presence of a base, and then reacting the resulting reaction product with an amine salt or an amine compound to obtain a fluorine-containing isoxazole compound represented by the following general formula (2): [Chemistry 18] (In the above general formulas (2), (5) and (15), R represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X is a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, A １ , A ２ and A 3 each independently represents a hydrogen atom, a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, or a heterocycle; A ４ Is = C ｎ H ２ｎ represents an alkylene group represented by the formula: n is an integer from 1 to 20.

14. 5. A method for producing a fluorine-containing isoxazole compound according to claim 4, comprising the steps of reacting a fluorine-containing carbonyl compound represented by the following general formula (10) with an alcohol, reacting the obtained reaction product with a compound represented by the following general formula (5) or a salt thereof in the presence of a base, and then reacting the resultant reaction product with an amine salt or an amine compound, thereby obtaining a fluorine-containing isoxazole compound represented by the following general formula (2): 【Chemistry 19】 (In the above general formulas (2), (5), and (10), R represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, X is a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, A １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A ４ Is = C ｎ H ２ｎ represents an alkylene group represented by the formula: n is an integer from 1 to 20, W ＋ represents an ammonium cation, an imidazolium cation, a pyridinium cation, a quinuclidium cation, or a phosphonium cation.

15. 5. A method for producing a fluorine-containing isoxazole compound according to claim 4, comprising the steps of: carbonylating a fluoroisobutene derivative represented by the following general formula (11) in the presence of a nucleophile, further reacting the resulting reaction product with an alcohol, reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof in the presence of a base, and then reacting the resulting reaction product with an amine salt or an amine compound, thereby obtaining a fluorine-containing isoxazole compound represented by the following general formula (2): 【Chemistry 20】 (In the above general formulas (2), (5) and (11), R and R' each independently represent a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X is a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, A １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; A ４ Is = C ｎ H ２ｎ represents an alkylene group represented by the formula: n is an integer from 1 to 20.

16. 5. A method for producing a fluorine-containing isoxazole compound according to claim 4, comprising the steps of: carbonylating a compound obtained by an elimination reaction of a fluoroisobutane derivative represented by the following general formula (12) in the presence of a nucleophile; further reacting the resulting reaction product with an alcohol; reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof in the presence of a base; and then reacting the resulting reaction product with an amine salt or an amine compound, thereby obtaining a fluorine-containing isoxazole compound represented by the following general formula (2): 【Chemistry 21】 (In the above general formulas (2), (5) and (12), R and R' each independently represent a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X represents a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ -NA ４ or a heterocycle, Y is a halogen atom, —OB １ , -SO ｍ B １ or -NB １ B ２ represents m is an integer from 0 to 3; A １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; A ４ Is = C ｎ H ２ｎ represents an alkylene group represented by the formula: n is an integer from 1 to 20, B １ and B ２ each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.

17. 4. A method for producing a fluorine-containing isoxazole compound according to claim 3, comprising the steps of reacting a fluorine-containing carbonyl compound represented by the following general formula (10) with a hydroxylamine represented by the following general formula (7) or a salt thereof, and further reacting the obtained reaction product with a compound represented by the following general formula (5) or a salt thereof, thereby obtaining a fluorine-containing isoxazole compound represented by the following general formula (3): 【Chemistry 22】 (In the above general formulas (3), (5) and (10), X is a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, A １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; A ４ Is = C ｎ H ２ｎ represents an alkylene group represented by the formula: n is an integer from 1 to 20, W ＋ represents an ammonium cation, an imidazolium cation, a pyridinium cation, a quinuclidium cation, or a phosphonium cation.

18. 4. A method for producing a fluorine-containing isoxazole compound according to claim 3, comprising the steps of: carbonylating a fluoroisobutene derivative represented by the following general formula (11) in the presence of a nucleophile; further reacting the resulting fluoroisobutene derivative with a hydroxylamine represented by the following general formula (7) or a salt thereof; and then reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof to obtain a fluorine-containing isoxazole compound represented by the following general formula (3). 【Chemistry 23】 (In the above general formulas (3), (5) and (11), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X is a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, A １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; A ４ Is = C ｎ H ２ｎ represents an alkylene group represented by the formula: n is an integer from 1 to 20.

19. 4. A method for producing a fluorine-containing isoxazole compound according to claim 3, comprising the steps of: carbonylating a fluoroisobutane derivative represented by the following general formula (12) in the presence of a nucleophile; further reacting the fluoroisobutane derivative with a hydroxylamine represented by the following general formula (7) or a salt thereof; and then reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof to obtain a fluorine-containing isoxazole compound represented by the following general formula (3): 【Chemistry 24】 (In the above general formulas (3), (5) and (12), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X is a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ -NA ４ or a heterocycle, Y is a halogen atom, —OB １ , -SO ｍ B １ or -NB １ B ２ represents m is an integer from 0 to 3; A １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; A ４ Is = C ｎ H ２ｎ represents an alkylene group represented by the formula: n is an integer from 1 to 20, B １ and B ２ each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.

20. 4. A method for producing a fluorine-containing isoxazole compound according to claim 3, comprising a step of reacting a fluoroisobutene derivative represented by the following general formula (11), a compound represented by the following general formula (5) or a salt thereof, and a hydroxylamine represented by the following general formula (7) or a salt thereof to obtain a fluorine-containing isoxazole compound represented by the following general formula (4): 【Chemistry 25】 (In the above general formulas (4), (5) and (11), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X is a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ (OA ２ ), -NA １ A ２ , -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, A １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; A ４ Is = C ｎ H ２ｎ represents an alkylene group represented by the formula: n is an integer from 1 to 20.

21. The method for producing a fluorine-containing isoxazole compound according to claim 3, comprising a step of reacting a fluoroisobutene derivative represented by the following general formula (11) with a hydroxylamine represented by the following general formula (7) or a salt thereof to obtain a fluorine-containing isoxazole compound represented by the following general formula (4-1): 【Chemistry 26】 (In the above general formulas (4-1) and (11), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.

22. 4. A method for producing a fluorine-containing isoxazole compound according to claim 3, comprising a step of reacting a fluoroisobutane derivative represented by the following general formula (12), a compound represented by the following general formula (5) or a salt thereof, and a hydroxylamine represented by the following general formula (7) or a salt thereof to obtain a fluorine-containing isoxazole compound represented by the following general formula (4): 【Chemistry 27】 (In the above general formulas (4), (5) and (12), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; X is a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, Y is a halogen atom, —OB １ , -SO ｍ B １ or -NB １ B ２ represents m is an integer from 0 to 3; A １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; A ４ Is = C ｎ H ２ｎ represents an alkylene group represented by the formula: n is an integer from 1 to 20, B １ and B ２ each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.

23. The method for producing a fluorine-containing isoxazole compound according to claim 3, comprising a step of reacting a fluoroisobutane derivative represented by the following general formula (12) with a hydroxylamine represented by the following general formula (7) to obtain a fluorine-containing isoxazole compound represented by the following general formula (4-1): 【Chemistry 28】 (In the above general formulas (4-1) and (12), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; Y is a halogen atom, —OB １ , -SO ｍ B １ or -NB １ B ２ represents m is an integer from 0 to 3; B １ and B ２ each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.

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