Preparation method of two methyl substituted 2-oxo-3-cyclopentene-1-carboxylate compounds and dicarboxylate compounds used for preparation

Abstract

The present invention provides a method for preparing a compound of the following general formula (2): wherein R 1 represents a monovalent hydrocarbon group having 1 to 10 carbon atoms, and R 3 represents a hydrogen atom or a methyl group, the method comprising: making a compound of the following general formula (1): wherein R 1 and R 2 independently represent a monovalent hydrocarbon group having 1 to 10 carbon atoms, R 3 represents a hydrogen atom or a methyl group, and the wavy bond represents an E-configuration, a Z-configuration or a mixture thereof, and a Dieckmann condensation reaction is carried out in the presence of a base to form the compound (2).

Description

Technical Field

[0001] The present invention relates to a method for preparing a 5,5-dimethyl-2-oxo-3-cyclopentene-1-carboxylate compound and a 3,5,5-trimethyl-2-oxo-3-cyclopentene-1-carboxylate compound from a 3,3-dimethyl-1-butene-1,4-dicarboxylate compound and a 1,3,3-trimethyl-1-butene-1,4-dicarboxylate compound, respectively. The present invention also relates to a 1,3,3-trimethyl-1-butene-1,4-dicarboxylate compound. Background Art

[0002] 5,5-dimethyl-2-oxo-3-cyclopentene-1-carboxylate compounds and 3,5,5-trimethyl-2-oxo-3-cyclopentene-1-carboxylate compounds are useful intermediates for synthesizing biologically active substances and pheromones having a 5-membered ring. For example, α-necrodyl compounds, i.e., a group of compounds having a (3,4,5,5-tetramethyl-2-cyclopentenyl)methyl group, and γ-necrodyl compounds, i.e., a group of compounds having a (2,2,3,4-tetramethyl-3-cyclopentenyl)methyl group, exist naturally as biologically active substances. These compounds can be derived from 3,5,5-trimethyl-2-oxo-3-cyclopentene-1-carboxylate compounds. Specifically, 3,5,5-trimethyl-2-oxo-3-cyclopentene-1-carboxylate compounds are useful intermediates for synthesizing methyl (1RS,4RS)-(3,4,5,5-tetramethyl-2-cyclopentenyl)isobutyrate, which is the sex pheromone of grape mealybug (scientific name: Pseudococcus maritimus), and methyl (2,2,3,4-tetramethyl-3-cyclopentenyl)isobutyrate, which is the sex pheromone of spherical mealybug (scientific name: Nipaecoccus viridis) (Non-patent Documents 1 and 2 listed below).

[0003] In order to prepare a 5,5-dimethyl-2-oxo-3-cyclopentene-1-carboxylate compound, it was reported that 4,4-dimethylcyclopentene-2-ene-1-one reacts with a base to form an enolate, which is then reacted with methyl cyanoformate to obtain 5,5-dimethyl-2-oxo-3-cyclopentene-1-carboxylic acid methyl ester (Non-patent document 3 listed below).

[0004] List of existing technologies

[0005] [Non-patent document 1] JG Millar et al., J. Agric. Food Chem., 2010, 58, 4977-4982.

[0006] [Non-patent document 2] A. Levi-Zada et al., J. Chem. Ecol., 2019, 45, 455-463.

[0007] [Non-patent document 3] J. Richers et al., Chem. Eur. J., 2017, 23, 3178-3183. Summary of the invention

[0008] As described above, as described in Non-Patent Document 3 by Richers et al., a method for preparing a 5,5-dimethyl-2-oxo-3-cyclopentene-1-carboxylate compound is known. However, in Non-Patent Document 3, the methoxycarbonylation of 4,4-dimethyl-2-cyclopentene-1-one is carried out at -78°C, so special equipment for low-temperature reactions is required. In this method, the C-methoxycarbonylation required in the reaction of the prepared enolate with methyl cyanoformate competes with the undesired O-methoxycarbonylation, so the target compound may not be obtained in high yield. In addition, harmful cyanide ions are formed from an equal amount of methyl cyanoformate, so careful post-treatment is required. Therefore, considering safety, this method is disadvantageous.

[0009] The present invention has been accomplished under these circumstances, and its object is to provide 5,5-dimethyl-2-oxo-3-cyclopentene-1-carboxylate compounds and 3,5,5-trimethyl-2-oxo-3-cyclopentene-1-carboxylate compounds safely and in high yield without using a low-temperature reaction apparatus.

[0010] After intensive research, the present inventors found that the Dieckmann condensation of 3,3-dimethyl-1-butene-1,4-dicarboxylate compound with a base can give 5,5-dimethyl-2-oxo-3-cyclopentene-1-carboxylate compound in high yield, and thus completed the present invention.

[0011] As another result of intensive studies, the present inventors also found that Dieckmann condensation of a 1,3,3-trimethyl-1-butene-1,4-dicarboxylate compound with a base gives a 3,5,5-trimethyl-2-oxo-3-cyclopentene-1-carboxylate compound in high yield, and thus completed the present invention.

[0012] According to one aspect of the present invention, there is provided a method for preparing a compound of the following general formula (2):

[0013]

[0014] Where R 1 represents a monovalent hydrocarbon group having 1 to 10 carbon atoms, and R 3 represents a hydrogen atom or a methyl group,

[0015] The method comprises:

[0016] The following compound of general formula (1):

[0017]

[0018] Where R 1 represents a monovalent hydrocarbon group having 1 to 10 carbon atoms, R 2 represents a monovalent hydrocarbon group having 1 to 10 carbon atoms, R 3 As defined above, and the wavy bond represents the E-configuration, the Z-configuration, or a mixture thereof,

[0019] The Dieckmann condensation reaction is carried out in the presence of a base to form compound (2).

[0020] According to another aspect of the present invention, the aforementioned method for preparing compound (2) further comprises:

[0021] The phosphonate anion is generated from the phosphonate compound of the following general formula (3):

[0022]

[0023] Where R 2 and R 3 As defined above, and R 4 represents a monovalent hydrocarbon group or a halogenated alkyl group having 1 to 10 carbon atoms,

[0024] A Horner-Wordsworth-Emmons reaction is carried out with an aldehyde compound of the following general formula (4):

[0025]

[0026] Where R 1 As defined above,

[0027] to form compound (1).

[0028] According to another aspect of the present invention, a 1,3,3-trimethyl-1-butene-1,4-dicarboxylate compound of the following general formula (5) is also provided:

[0029]

[0030] Where R 1 and R 2 independently represent a monovalent hydrocarbon group having 1 to 10 carbon atoms, R 3 represents a hydrogen atom or a methyl group, and the wavy bond represents the E-configuration, the Z-configuration or a mixture thereof.

[0031] The present invention provides a 3,3-dimethyl-1-butene-1,4-dicarboxylate compound and a 1,3,3-trimethyl-1-butene-1,4-dicarboxylate compound, which are used as intermediates for preparing a 5,5-dimethyl-2-oxo-3-cyclopentene-1-carboxylate compound and a 3,5,5-trimethyl-2-oxo-3-cyclopentene-1-carboxylate compound, respectively. According to the present invention, the 5,5-dimethyl-2-oxo-3-cyclopentene-1-carboxylate compound and the 3,5,5-trimethyl-2-oxo-3-cyclopentene-1-carboxylate compound are prepared in high yield, no harmful byproducts are formed, and no low-temperature reaction equipment is required. Surprisingly, the target compound can be produced convergently from a (E)-3,3-dimethyl-1-butene-1,4-dicarboxylate compound and a (E)-1,3,3-trimethyl-1-butene-1,4-dicarboxylate compound, thereby obtaining a 5,5-dimethyl-2-oxo-3-cyclopentene-1-carboxylate compound and a 3,5,5-trimethyl-2-oxo-3-cyclopentene-1-carboxylate compound in high yield. DETAILED DESCRIPTION

[0032] Embodiments of the present invention will be described in detail below. It should be understood that the present invention is not limited to or by these embodiments. The intermediates, reagents and target compounds represented by chemical formulae in this specification may have some stereoisomers. Unless otherwise indicated, each chemical formula should be interpreted as representing all possible isomers. Isomers can be used alone or in combination.

[0033] A. The following will first describe the 5,5-dimethyl-2-oxo-3-cyclopentene-1-carboxylate compound and the 3,5,5-trimethyl-2-oxo-3-cyclopentene-1-carboxylate compound prepared in the method according to the present invention.

[0034] The 5,5-dimethyl-2-oxo-3-cyclopentene-1-carboxylate compound and the 3,5,5-trimethyl-2-oxo-3-cyclopentene-1-carboxylate compound are collectively represented by the following general formula (2), and the 5,5-dimethyl-2-oxo-3-cyclopentene-1-carboxylate compound and the 3,5,5-trimethyl-2-oxo-3-cyclopentene-1-carboxylate compound may be hereinafter referred to as simply “compound (2)”.

[0035]

[0036] R in the general formula (2) 1 represents a monovalent hydrocarbon group having 1 to 10 carbon atoms, preferably 1 to 4 carbon atoms.

[0037] R 1Examples of the monovalent hydrocarbon group include straight-chain saturated hydrocarbon groups such as methyl groups, ethyl groups, n-propyl groups, n-butyl groups, n-pentyl groups, n-hexyl groups, n-heptyl groups, n-octyl groups, n-nonyl groups, and n-decyl groups; branched saturated hydrocarbon groups such as isopropyl groups, 2-methylbutyl groups, and tert-butyl groups; cyclic saturated hydrocarbon groups such as cyclopropyl groups, cyclobutyl groups, cyclopentyl groups, cyclohexyl groups, and cyclopentylmethyl groups; straight-chain unsaturated hydrocarbon groups such as vinyl groups, allyl groups, and ethynyl groups; branched unsaturated hydrocarbon groups such as isopropenyl groups and 2-methyl-2-propenyl groups; cyclic unsaturated hydrocarbon groups such as phenyl groups, tolyl groups, dimethylphenyl groups, benzyl groups, and phenethyl groups; and isomers thereof. A portion of the hydrogen atoms in the hydrocarbon group may be substituted by a monovalent hydrocarbon group having 1 to 9 carbon atoms.

[0038] R in the general formula (2) 3 represents a hydrogen atom or a methyl group. 3 When R is a hydrogen atom, the general formula (2) represents a 5,5-dimethyl-2-oxo-3-cyclopentene-1-carboxylate compound. 3 When it is a methyl group, the general formula (2) represents a 3,5,5-trimethyl-2-oxo-3-cyclopentene-1-carboxylate compound.

[0039] Specific examples of compound (2) include 5,5-dimethyl-2-oxo-3-cyclopentene-1-carboxylate compounds such as 5,5-dimethyl-2-oxo-3-cyclopentene-1-carboxylic acid methyl ester, 5,5-dimethyl-2-oxo-3-cyclopentene-1-carboxylic acid ethyl ester, 5,5-dimethyl-2-oxo-3-cyclopentene-1-carboxylic acid tert-butyl ester and 5,5-dimethyl-2-oxo-3-cyclopentene-1-carboxylic acid phenyl ester; and 3,5,5-trimethyl-2-oxo-3-cyclopentene-1-carboxylate compounds, such as 3,5,5-trimethyl-2-oxo-3-cyclopentene-1-carboxylic acid methyl ester, 3,5,5-trimethyl-2-oxo-3-cyclopentene-1-carboxylic acid ethyl ester, 3,5,5-trimethyl-2-oxo-3-cyclopentene-1-carboxylic acid tert-butyl ester and 3,5,5-trimethyl-2-oxo-3-cyclopentene-1-carboxylic acid phenyl ester.

[0040] B. Next, the method for producing compound (2) according to the present invention will be described below.

[0041] The present inventors have considered a synthetic plan for compound (2) as described below.

[0042]

[0043] In the reaction formula of retrosynthetic analysis, open arrows represent transformations in retrosynthetic analysis. Unless otherwise specifically stated herein, wavy bonds in chemical structures represent E-configuration, Z-configuration or a mixture thereof.

[0044] Step B' The target compound of the present invention, compound (2), i.e., 5,5-dimethyl-2-oxo-3-cyclopentene-1-carboxylate compound and 3,5,5-trimethyl-2-oxo-3-cyclopentene-1-carboxylate compound, is considered to be synthesized by subjecting compound (1), i.e., 3,3-dimethyl-1-butene-1,4-dicarboxylate compound and 1,3,3-trimethyl-1-butene-1,4-dicarboxylate compound to Dieckmann condensation reaction in the presence of a base. 5,5-dimethyl-2-oxo-3-cyclopentene-1-carboxylate compound and 3,5,5-trimethyl-2-oxo-3-cyclopentene-1-carboxylate compound are hereinafter referred to as "compound (1)". The preferred geometrical isomer of compound (1) is considered to be Z-configuration because Z-configuration is suitable for ring formation, that is, two carbon atoms to be bonded in ring formation are present on the same side of the double bond.

[0045]

[0046] In the formula above, the arrows indicate where the two carbon atoms will newly bond.

[0047] The target compound of step A', compound (1) is considered to be synthesized in a Horner-Wordsworth-Emmons reaction (hereinafter also referred to as "HWE reaction") between a phosphonate anion generated from a phosphonate compound of the general formula (3) shown in the above reaction formula and an aldehyde compound of the general formula (4) shown in the above reaction formula.

[0048] Taking the above retrosynthetic analysis into consideration, the reaction formula of an embodiment of the present invention is as follows.

[0049]

[0050] Steps A and B as an embodiment of the present invention will be described in detail below.

[0051] First, step B is performed, wherein the target compound of the present invention, compound (2), is synthesized. Then, step A is described, wherein the starting material in step B is synthesized. In the description of step A, a method for synthesizing a 1,3,3-trimethyl-1-butene-1,4-dicarboxylate compound of the following general formula (5) will also be described, wherein R 3 It is a compound (1) having a methyl group.

[0052]

[0053] [1] Step B

[0054] Hereinafter, step B in which compound (2) is synthesized will be described. As shown in the following chemical reaction formula, compound (2) is synthesized by subjecting compound (1) to Dieckmann condensation in the presence of a base.

[0055]

[0056] R in the general formula (1) 1 represents a monovalent hydrocarbon group having 1 to 10 carbon atoms. 2 represents a monovalent hydrocarbon group having 1 to 10, preferably 1 to 4, carbon atoms. 3 With R defined in the general formula (2) 3 same.

[0057] Specific examples of compound (1) include (E)-3,3-dimethyl-1-butene-1,4-dicarboxylate compounds such as (E)-3,3-dimethyl-1-butene-1,4-dicarboxylic acid diethyl ester, (E)-5-ethoxycarbonyl-4,4-dimethyl-2-pentenoic acid tert-butyl ester and (E)-4,4-dimethyl-5-phenoxycarbonyl-2-pentenoic acid ethyl ester; (Z)-3,3-dimethyl-1-butene-1,4-dicarboxylate compounds such as (Z)-3,3-dimethyl-1-butene-1,4-dicarboxylate diethyl ester, (Z)-5-ethoxycarbonyl-4,4-dimethyl-2-pentenoic acid tert-butyl ester and (Z)-4,4-trimethyl-5-phenoxycarbonyl-2-pentenoic acid ethyl ester; )-1,3,3-trimethyl-1-butene-1,4-dicarboxylate compounds, such as (E)-1,3,3-trimethyl-1-butene-1,4-dicarboxylic acid diethyl ester, (E)-5-ethoxycarbonyl-2,4,4-trimethyl-2-pentenoic acid tert-butyl ester and (E)-2,4,4-trimethyl-5-phenoxycarbonyl-2-pentenoic acid ethyl ester; and (Z)-1,3,3-trimethyl-1-butene-1,4-dicarboxylate compounds, such as (Z)-1,3,3-trimethyl-1-butene-1,4-dicarboxylic acid diethyl ester, (Z)-5-ethoxycarbonyl-2,4,4-trimethyl-2-pentenoic acid tert-butyl ester and (Z)-2,4,4-trimethyl-5-phenoxycarbonyl-2-pentenoic acid ethyl ester.

[0058] The 1,3,3-trimethyl-1-butene-1,4-dicarboxylate compound of the general formula (5) is one in which R 3Compounds (1) having a methyl group, such as (Z)-1,3,3-trimethyl-1-butene-1,4-dicarboxylic acid diethyl ester and (E)-1,3,3-trimethyl-1-butene-1,4-dicarboxylic acid diethyl ester, are preferably used to prepare 3,5,5-trimethyl-2-oxo-3-cyclopentene-1-carboxylate compounds, which are useful as intermediates for preparing sex pheromones of grape mealybugs and spherical mealybugs.

[0059] Specific examples of the 1,3,3-trimethyl-1-butene-1,4-dicarboxylate compound (5) include a (Z)-1,3,3-trimethyl-1-butene-1,4-dicarboxylate compound of the following general formula (Z)-(5), a (E)-1,3,3-trimethyl-1-butene-1,4-dicarboxylate compound of the following general formula (E)-(5), and both.

[0060]

[0061] The 1,3,3-trimethyl-1-butene-1,4-dicarboxylate compound (5) can be synthesized by the following HWE reaction.

[0062] Compound (2) can be synthesized by reacting Compound (1) in the presence of a base in a solvent.

[0063] Examples of the base used to prepare compound (2) include metal alkoxides such as sodium tert-butoxide, potassium tert-butoxide, sodium methoxide, potassium methoxide, sodium ethoxide and potassium ethoxide; alkyl lithiums such as n-butyl lithium and tert-butyl lithium; metal hydrides such as lithium hydride, sodium hydride and potassium hydride; metal acetylates such as lithium acetylate and sodium acetylate; metal amides such as lithium diisopropylamide and sodium bis(trimethylsilyl)amide; and amines such as 1,8-diazabicyclo[5.4.0]-7-undecene, 1,5-diazabicyclo[4.3.0]-5-nonene and N,N-diisopropylethylamine. In view of reactivity, metal alkoxides such as sodium tert-butoxide, potassium tert-butoxide, sodium methoxide and sodium ethoxide are preferred.

[0064] The amount of the base to be used is preferably 1.0 to 5.0 mol, more preferably 1.0 to 3.0 mol, per mol of compound (1), in view of reactivity.

[0065] Examples of the solvent used in the preparation of compound (2) include ether solvents such as tetrahydrofuran, 4-methyltetrahydropyran, diethyl ether and tert-butyl methyl ether; hydrocarbon solvents such as toluene, xylene and hexane; and polar solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile, dichloromethane and chloroform. In view of reactivity, ether solvents such as tetrahydrofuran and hydrocarbon solvents such as toluene are preferred.

[0066] If necessary, the solvent may be used alone or in combination. In view of reactivity and solubility, a mixed solvent of tetrahydrofuran and toluene is preferred. The solvent may be a commercially available product.

[0067] The amount of the solvent used varies depending on the production scale, and is preferably 200 g to 4,000 g per mol of the compound (1) in consideration of the reaction rate.

[0068] The reaction temperature for preparing compound (2) varies depending on the solvent used, and is preferably 0°C to 150°C, more preferably 30°C to 80°C, in view of reactivity and isomerization rate.

[0069] The reaction time for preparing compound (2) varies depending on the solvent to be used and / or the reaction scale, and is preferably 0.1 to 20 hours.

[0070] In the embodiment of preparing compound (2), as shown in the following chemical reaction formula, the 3,5,5-trimethyl-2-oxo-3-cyclopentene-1-carboxylate compound (i.e., R 3 The compound (2) is a methyl group and can be prepared by making the following 1,3,3-trimethyl-1-butene-1,4-dicarboxylate compound (5) (Z / E=94:6) (i.e. R 3 The compound (1) having a methyl group is synthesized by Dieckmann condensation in the presence of a base. The 1,3,3-trimethyl-1-butene-1,4-dicarboxylate compound (5) is synthesized by the following Z-selective HWE reaction.

[0071]

[0072] It is expected that the Dieckmann condensation will not proceed with the E-configuration (E)-1,3,3-trimethyl-1-butene-1,4-dicarboxylate compound ((E)-(5)). Surprisingly, it has been found that the E-configuration undergoes the Dieckmann condensation to convergently provide the target compound 3,5,5-trimethyl-2-oxo-3-cyclopentene-1-carboxylate compound (6). In order to verify this phenomenon, the E-configuration-rich 1,3,3-trimethyl-1-butene-1,4-dicarboxylate compound (5) (Z / E=33:67) was subjected to a condensation reaction to find that the target compound 3,5,5-trimethyl-2-oxo-3-cyclopentene-1-carboxylate compound (6) is produced from the E-configuration. Due to this discovery, it is not necessary to conduct the HWE reaction in a Z-selective manner, and the 3,5,5-trimethyl-2-oxo-3-cyclopentene-1-carboxylate compound (6) can be synthesized more efficiently.

[0073] In another embodiment of preparing compound (2), as shown in the following chemical reaction formula, the 5,5-dimethyl-2-oxo-3-cyclopentene-1-carboxylate compound (i.e., R 3 The compound (2) is a hydrogen atom and can be prepared by making a 4,4-dimethyl-2-hexene dicarboxylate compound (R 3 is a compound containing hydrogen atoms) by Dieckmann condensation in the presence of a base.

[0074]

[0075] In the above condensation reaction, in addition to the target compound 5,5-dimethyl-2-oxo-3-cyclopentene-1-carboxylate compound, a 3,3-dimethyl-5-oxo-1-cyclopentene-1-carboxylate compound of the following general formula (11) which is not the target compound may also be formed.

[0076]

[0077] This may be due to the following reaction scheme.

[0078]

[0079] In this scheme, the rightward harpoon on the leftward harpoon represents a reversible equilibrium; R 1 and R 2 As defined in compound (1); R represents an alkyl group; and M + Represents the cationic part.

[0080] In this scheme, the base RO - M + The conjugated double bond of the 3,3-dimethyl-1-butene-1,4-dicarboxylate compound (8) is connected to and separated from it, thereby isomerizing the double bond to promote the Dieckmann condensation of the Z-configuration, thereby forming the target compound 5,5-dimethyl-2-oxo-3-cyclopentene-1-carboxylate compound (9) (route a).

[0081] At the same time, when the base RO - M + After connecting to the conjugated double bond of the 3,3-dimethyl-1-butene-1,4-dicarboxylate compound (8), the carbonyl carbon atom in the resulting enolate is attacked to form a cyclopentanone compound (route b); the OR group in the cyclopentanone compound is eliminated to form a 3,3-dimethyl-5-oxo-1-cyclopentene-1-carboxylate compound (11) which is not the target compound.

[0082] As mentioned above, when R in the general formula (1) 3When it is a hydrogen atom (ie, in the case of 3,3-dimethyl-1-butene-1,4-dicarboxylate compound (8)), in addition to the reaction envisioned in route a, a side reaction route b also occurs.

[0083] On the other hand, when R in the general formula (1) 3 In the case of a methyl group (i.e., in the case of 1,3,3-trimethyl-1-butene-1,4-dicarboxylate compound (5)), the resulting cyclopentanone compound has no hydrogen atom on the carbon atom sandwiched between the keto group and the ester group, and therefore, the OR group does not leave and equilibrium does not occur, which is different from the equilibrium Z shown in the above scheme. According to the above-mentioned inferred theory, the path a appears mainly to provide its product.

[0084] Therefore, the method according to the invention is particularly applicable to compounds of the general formula (1) in which R 3 is a methyl group (i.e., 1,3,3-trimethyl-1-butene-1,4-dicarboxylate compound (5)). When 3,3-dimethyl-1-butene-1,4-dicarboxylate compound (8) contains its E configuration in a larger proportion, the unwanted 3,3-dimethyl-5-oxy-1-cyclopentene-1-carboxylate compound (11) appears in a larger proportion, and vice versa. Therefore, when R in the general formula (1) 3 When it is a hydrogen atom, it is preferable to use a 3,3-dimethyl-1-butene-1,4-dicarboxylate compound (8) having a Z-rich configuration.

[0085] [2] Step A

[0086] Next, step A in which compound (1) is synthesized will be described. As shown in the following chemical reaction formula, compound (1) is obtained by a HWE reaction between a phosphonate anion derived from a phosphonate compound (3) and an aldehyde compound (4).

[0087]

[0088] R in the general formula (3) 2 As defined in general formula (1).

[0089] R in the general formula (3) 3 As defined in general formula (2). R in general formula (3) 4 represents a monovalent hydrocarbon group or a halogenated alkyl group having 1 to 10, preferably 1 to 6 carbon atoms.

[0090] R 4Examples of the monovalent hydrocarbon group include straight-chain saturated hydrocarbon groups such as methyl groups, ethyl groups, n-propyl groups, n-butyl groups, n-pentyl groups, n-hexyl groups, n-heptyl groups, n-octyl groups, n-nonyl groups, and n-decyl groups; branched saturated hydrocarbon groups such as isopropyl groups, 2-methylbutyl groups, and tert-butyl groups; cyclic saturated hydrocarbon groups such as cyclopropyl groups, cyclobutyl groups, cyclopentyl groups, cyclohexyl groups, and cyclopentylmethyl groups; straight-chain unsaturated hydrocarbon groups such as vinyl groups, allyl groups, and ethynyl groups; branched unsaturated hydrocarbon groups such as isopropenyl groups and 2-methyl-2-propenyl groups; cyclic unsaturated hydrocarbon groups such as phenyl groups, tolyl groups, dimethylphenyl groups, benzyl groups, and phenethyl groups; and isomers thereof. A portion of the hydrogen atoms in the hydrocarbon group may be substituted by a monovalent hydrocarbon group having 1 to 9 carbon atoms.

[0091] R 4 Examples of the monovalent haloalkyl group include haloalkyl groups such as a trifluoroethyl group, which are used in the Still-Gennari process and other processes capable of performing a Z-selective HWE reaction.

[0092] Examples of the phosphonate compound (3) include 2-phosphonopropionate compounds such as triethyl 2-phosphonopropionate and ethyl 2-(diphenylphosphono)propionate; phosphonoacetate compounds such as triethyl phosphonoacetate and ethyl diphenylphosphonoacetate; and phosphonate compounds used in the Still-Gennari method such as bis(2,2,2-trifluoroethyl)(methoxycarbonylmethyl)phosphonate.

[0093] The phosphonate compound (3) may be a commercially available product or may be synthesized in-house. For example, the compound may be synthesized by subjecting a haloalkyl group and a phosphite to an Arbuzov reaction.

[0094] R in the aldehyde compound (4) 1 R defined in the general formula (1) 1 same.

[0095] Examples of the aldehyde compound (4) include 3,3-dimethyl-4-oxobutyrate compounds such as methyl 3,3-dimethyl-4-oxobutyrate, ethyl 3,3-dimethyl-4-oxobutyrate, tert-butyl 3,3-dimethyl-4-oxobutyrate, and phenyl 3,3-dimethyl-4-oxobutyrate.

[0096] The aldehyde compound (4) may be a commercially available product or may be synthesized in-house. The compound may be synthesized in any known method or by reacting an enamine derived from isobutylaldehyde with a haloacetic acid ester.

[0097] The compound (1) can be synthesized by reacting a phosphonate compound (3) in the presence of a base in a solvent to form a phosphonate anion, and subjecting the phosphonate anion to a Horner-Wordsworth-Emmons reaction with an aldehyde compound (4).

[0098] Examples of the base used in forming the phosphonate anion include metal alkoxides such as sodium tert-butoxide, potassium tert-butoxide, sodium methoxide, potassium methoxide, sodium ethoxide, and potassium ethoxide; alkyl lithiums such as n-butyl lithium and tert-butyl lithium; metal hydrides such as lithium hydride, sodium hydride, and potassium hydride; metal acetylates such as lithium acetylate and sodium acetylate; metal amides such as lithium diisopropylamide and sodium bis(trimethylsilyl)amide; and amines such as 1,8-diazabicyclo[5.4.0]-7-undecene, 1,5-diazabicyclo[4.3.0]-5-nonene, and N,N-diisopropylethylamine. In view of suppressing the formation of by-products, metal hydrides such as sodium hydride, and metal acetylates such as lithium acetylate and sodium acetylate are preferred.

[0099] If necessary, the base may be used alone or in combination. The base may be a commercially available product.

[0100] The amount of the base to be used is preferably 0.8 mol to 1.3 mol per mol of the phosphonate compound (3) in view of reactivity and suppression of by-product formation.

[0101] If necessary, an alkali metal halide such as lithium chloride or sodium iodide may be added to prepare the phosphonate anion.

[0102] The amount of the alkali metal halide to be used is preferably 0.01 mol to 1.3 mol per mol of the phosphonate compound (3) in view of reactivity and cost.

[0103] Examples of solvents that form phosphonate anions include ether solvents such as tetrahydrofuran, 4-methyltetrahydrofuran, diethyl ether, and methyl tert-butyl ether; hydrocarbon solvents such as toluene, xylene, and hexane; polar solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile, dichloromethane, and chloroform. Tetrahydrofuran, acetonitrile, N,N-dimethylformamide, and N,N-dimethylacetamide, which are widely used in HWE reactions, are particularly preferred. Hydrocarbon solvents are also preferred because sodium acetylide used as a base dissolves in xylene.

[0104] If necessary, the solvent may be used alone or in combination. In view of reactivity and solubility, a mixed solvent of tetrahydrofuran and xylene is preferred. The solvent may be a commercially available product.

[0105] The amount of the solvent used varies depending on the production scale, and is preferably 200 g to 4,000 g per mol of the phosphonate compound (3) in consideration of the reaction rate.

[0106] The reaction temperature for the phosphonate anion formation varies depending on the solvent to be used, and is preferably -78°C to 150°C, more preferably 0°C to 80°C, in view of reactivity and suppression of formation of by-products.

[0107] The reaction time for the phosphonate anion formation varies depending on the solvent to be used and / or the reaction scale, and is preferably 0.1 hour to 20 hours.

[0108] The amount of the aldehyde compound (4) used in the HWE reaction is preferably 0.7 mol to 1.3 mol per mol of the phosphonate compound (3) in consideration of reactivity and cost.

[0109] The solvent and amount of solvent used in the HWE reaction may be the same or different than the solvent and amount of solvent used in forming the phosphonate anion.

[0110] The reaction temperature of the HWE reaction varies depending on the solvent to be used, and is preferably -78°C to 150°C, more preferably 0°C to 80°C, in view of reactivity and suppression of formation of by-products.

[0111] The reaction time of the HWE reaction varies depending on the solvent to be used and / or the reaction scale, and is preferably 0.1 hour to 20 hours.

[0112] If it is difficult to purify the HWE reaction product due to the similarity in polarity or boiling point between the HWE reaction product and the starting phosphonate compound (3) or aldehyde compound (4), another or additional phosphonate compound and / or another or additional aldehyde compound different from those used in the reaction may be added after the reaction to consume excess starting materials.

[0113] Examples of another or other phosphonate compounds for consuming excess starting materials include phosphonoacetic acid esters, such as triethyl 2-phosphonopropionate and triethyl phosphonoacetate. Examples of another or other aldehyde compounds for consuming excess starting materials include lower aldehydes, such as formaldehyde, acetaldehyde, propionyl aldehyde, butyraldehyde and isobutyraldehyde; and higher aldehydes, such as decanal, undecanal and dodecanal.

[0114] The amount of the another or other phosphonate compound and the another or other aldehyde compound to be used is preferably 0.01 mol to 0.5 mol per mol of the phosphonate compound (3), in view of reactivity and cost.

[0115] A specific example of the Z-selective HWE reaction is the case where R 2 is an ethyl group, R 3 is a methyl group, and R 4 is a phenyl group, and R 1 is an ethyl group, as shown in the following chemical reaction formula.

[0116]

[0117] A specific example of the HWE reaction that produces a mixture of Z-configuration and E-configuration is the following case: 2 and R 4 is an ethyl group, R 3 is a methyl group, and R 1 is an ethyl group, as shown in the following chemical reaction formula.

[0118]

[0119] The 1,3,3-trimethyl-1-butene-1,4-dicarboxylate compound (5) as the compound (1) for preparing the 3,5,5-trimethyl-2-oxo-3-cyclopentene-1-carboxylate compound can be synthesized, for example, by a HWE reaction between a phosphonate anion formed from a 2-phosphonopropionate compound and a 3,3-dimethyl-4-oxobutyrate compound.

[0120] Thus, provided are methods for preparing 3,3-dimethyl-1-butene-1,4-dicarboxylate and 1,3,3-trimethyl-1-butene-1,4-dicarboxylate compounds, which are useful intermediates for synthesizing 5,5-dimethyl-2-oxo-3-cyclopentene-1-carboxylate compounds and 3,5,5-trimethyl-2-oxo-3-cyclopentene-1-carboxylate compounds, each in high yield.

[0121] Example

[0122] The present invention will be described with reference to the following examples. It should be understood that the present invention is not limited to or by these examples.

[0123] Unless otherwise specified, the term "purity" used herein refers to the area percentage determined by gas chromatography (hereinafter also referred to as "GC"). The term "yield ratio" refers to the relative ratio of the area percentage determined by GC.

[0124] Yields were calculated from area percentages determined by GC.

[0125] Taking into account the purity (%GC) of the starting material and the product, the yield was calculated according to the following equation.

[0126] Yield (%)={[(mass of product obtained by reaction×%GC) / molecular weight of product]÷[(mass of starting material×%GC) / molecular weight of starting material]}×100.

[0127] The term "crude yield" refers to the yield of a crude product obtained without purification.

[0128] In the examples, the monitoring of the reaction and the calculation of the yield were carried out under the following GC conditions.

[0129] GC conditions: capillary gas chromatograph GC-2014 (Shimadzu Corporation); column: DB-5, 0.25 μm×0.25 mmφ×30 m; carrier gas: He (1.55 mL / min), detector: FID; column temperature: 100°C, increasing at a rate of 10°C / min to a maximum of 230°C.

[0130] Example 1: Preparation of 1,3,3-trimethyl-1-butene-1,4-dicarboxylic acid diethyl ester (5:R 1 =R 2 =Et;1:R 1 =R 2 =Et, R 3 =Me)

[0131]

[0132] wherein Ph represents a phenyl group, and Et represents an ethyl group.

[0133] Ethyl 2-(diphenoxyphosphinyl)propionate (139 g, 0.415 mol) (3:R 2 =Et; R 3 =Me; R 4 =Ph) and tetrahydrofuran (THF) (1,452 g) were placed in a reactor and cooled to 4 to 6°C while stirring. Sodium iodide (NaI) (99.5 g, 0.664 mol) was then added, followed by dropwise addition of 1,8-diazabicyclo[5.4.0]-7-undecene (DBU) (94.8 g, 0.622 mol) at 4 to 9°C. After completion of the dropwise addition, the mixture was stirred at 4 to 9°C for 30 minutes, and then ethyl 3,3-dimethyl-4-oxobutyrate (4:R) was added dropwise thereto at 4 to 9°C. 1 =Et) (140g, 0.887mol). After the addition was completed, the mixture was stirred at 57°C to 62°C for 8 hours and cooled to 4°C to 6°C. An aqueous ammonium chloride solution (804g: prepared from ammonium chloride (78g) and water (871g)) was added to quench the reaction, followed by the addition of ethyl acetate (871g). The resulting reaction mixture was phase separated. The resulting organic layer was then washed with brine (1,260g: prepared from sodium chloride (60g) and water (1,200g). The organic layer was concentrated under reduced pressure, and the concentrate was distilled under reduced pressure to obtain 1,3,3-trimethyl-1-butene-1,4-dicarboxylic acid diethyl ester (5:R 1 =R 2=Et) (70.5 g, 0.291 mol; Z / E=94:6), with a yield of 70.2%.

[0134] The following is the (Z)-1,3,3-trimethyl-1-butene-1,4-dicarboxylic acid diethyl ester (5:R 1 =R 2 =Et) spectral data.

[0135] NMR spectroscopy: 1 H-NMR (500MHz, CDCl3): δ1.19 (s, 6H), 1.23 (t, J = 7.3Hz, 3H), 1.30 (t, J = 7.3Hz, 3H), 1.90 (d, J =1.5Hz,3H),2.46(s,2H),4.10(q,J=7.3Hz,2H),4.19(q,J=7.3Hz,2H),5.62(q,J=1.5Hz,1H); 13 C-NMR (75.6MHz, CDCl3): δ14.07,14.24,22.58,27.73(2C),35.37,47.02,59.98,60.52,127.43,141.39,170.33,171.74.

[0136] Mass spectrum: EI-mass spectrum (70eV): m / z 242 (M + ),227,196,181,168,155,139,127,109,95,81,67,55,41,29.

[0137] Infrared absorption spectrum (NaCl): νmax 2980,1731,1452,1369,1342,1322,1246,1204,1100,1036,919,866,775.

[0138] The following is the spectrum data of (E)-1,3,3-trimethyl-1-butene-1,4-dicarboxylic acid diethyl ester prepared in this way.

[0139] NMR spectroscopy: 1 H-NMR (500MHz, CDCl3): δ1.21(t,J=7.3Hz,3H),1.27(t,J=7.3Hz,3H),1.28(s,6H),1.94(d,J =1.5Hz,3H),2.45(s,2H),4.09(q,J=7.3Hz,2H),4.16(q,J=7.3Hz,2H),6.83(q,J=1.5Hz,1H); 13C-NMR (75.6MHz, CDCl3): δ13.44,14.21(2C),27.93(2C),35.26,46.93,60.11,60.62,127.42,148.29,168.88,171.27.

[0140] Mass spectrum: EI-mass spectrum (70eV): m / z 242 (M + ),227,196,181,168,155,139,127,109,95,81,67,55,41,29.

[0141] Infrared absorption spectrum (NaCl): νmax 2980,1731,1452,1369,1342,1322,1246,1204,1100,1036,919,866,775.

[0142] Example 2: Preparation of 1,3,3-trimethyl-1-butene-1,4-dicarboxylic acid diethyl ester (5:R 1 =R 2 =Et;1:R 1 =R 2 =Et, R 3 =Me)

[0143]

[0144] wherein Et represents an ethyl group.

[0145] A solution of 0.00476 mol / g sodium acetylide in xylene (214 g, 1.02 mol) and THF (1,325 g) were placed in a reactor and cooled to 4 to 6°C while stirring. Then, triethyl 2-phosphonopropionate (3:R 2 =R 4 =Et; R 3 =Me) (242 g, 1.02 mol). After the addition was completed, the mixture was heated to 62° C. to 67° C. Subsequently, ethyl 3,3-dimethyl-4-oxobutyrate (4:R 1=Et) (140g, 0.887mol). After the addition was completed, the mixture was stirred at 62°C to 67°C for 1.5 hours. The mixture was then cooled to 37°C to 42°C, and isobutyraldehyde (25.5g, 0.353mol), sodium iodide (66.2g, 0.441mol) and 1,8-diazabicyclo[5.4.0]-7-undecene (53.8g, 0.353mol) were subsequently added thereto, and stirred at 37°C to 42°C for 1.5 hours. The mixture was then cooled to 4°C to 6°C, and an aqueous ammonium chloride solution (939g: prepared from ammonium chloride (85g) and water (854g)) was added to quench the reaction. Hexane (887g) was subsequently added. The resulting reaction mixture was phase separated. Then, the obtained organic layer was washed with an aqueous ammonium chloride solution (1,450 g, prepared from ammonium chloride (85 g), sodium chloride (33 g) and water (1,332 g)), and then washed with brine (1,399 g: prepared from sodium chloride (67 g) and water (1,332 g)). The organic layer was concentrated under reduced pressure, and the concentrate was distilled under reduced pressure to obtain diethyl 1,3,3-trimethyl-1-butene-1,4-dicarboxylate (5:R 1 =R 2 =Et) (177 g, 0.731 mol; Z / E=39:61), with a yield of 82.4%.

[0146] The thus prepared 1,3,3-trimethyl-1-butene-1,4-dicarboxylic acid diethyl ester (5:R 1 =R 2 =Et) are the same as those obtained in Example 1.

[0147] Example 3: Preparation of diethyl 3,3-dimethyl-1-butene-1,4-dicarboxylate (8:R 1 =R 2 =Et;1:R 1 =R 2 =Et, R 3 =H)

[0148]

[0149] wherein Ph and Et are as defined above.

[0150] Ethyl diphenylphosphonoacetate (3:R 2 =Et; R 3 =H; R 4=Ph) (52.1 g, 0.163 mol) and THF (455 g) were placed in a reactor and cooled to 4 to 6°C while stirring. Sodium iodide (39.0 g, 0.260 mol) was then added, followed by the dropwise addition of 1,8-diazabicyclo[5.4.0]-7-undecene (37.1 g, 0.244 mol) at 4 to 9°C. After the addition was complete, the mixture was stirred at 4 to 9°C for 30 minutes, and then ethyl 3,3-dimethyl-4-oxobutyrate (4:R) was added dropwise at 4 to 9°C. 1 =Et) (28.3g, 0.179mol). After the addition was completed, the mixture was stirred at room temperature for 4 hours and cooled to 4°C to 6°C. Then an aqueous ammonium chloride solution (358g: prepared from ammonium chloride (31g) and water (327g)) was added to quench the reaction, and then hexane (365g) was added. The resulting reaction mixture was phase separated. The resulting organic layer was then washed with brine (414g: prepared from sodium chloride (20g) and water (394g). The organic layer was concentrated under reduced pressure, and the concentrate was distilled under reduced pressure to obtain diethyl 3,3-dimethyl-1-butene-1,4-dicarboxylate (8:R 1 =R 2 =Et) (31.9 g, 0.140 mol; Z / E=78:22), with a yield of 86.0%.

[0151] The following is the (Z)-3,3-trimethyl-1-butene-1,4-dicarboxylic acid diethyl ester (8:R 1 =R 2 =Et) spectral data.

[0152] NMR spectroscopy: 1 H-NMR (500MHz, CDCl3): δ1.23(t,J=7.3Hz,3H),1.28(t,J=7.3Hz,3H),1.30(s,6H),2.72(s,2H) ),4.09(q,J=7.3Hz,2H),4.15(q,J=7.3Hz,2H),5.71(d,J=13.0Hz,1H),6.16(d,J=13.0Hz,1H); 13 C-NMR (75.6MHz, CDCl3): δ14.13, 14.21, 27.89 (2C), 35.60, 46.01, 60.00, 60.16, 119.41, 154.29, 166.23, 171.97.

[0153] Mass spectrum: EI-mass spectrum (70eV): m / z 228 (M +),213,199,183,167,154,141,126,109,95,81,67,55,41,29.

[0154] Infrared absorption spectrum (NaCl): νmax 2980, 2875, 1731, 1650, 1466, 1368, 1305, 1178, 1035, 982, 864, 722.

[0155] The following is the spectrum data of (E)-3,3-trimethyl-1-butene-1,4-dicarboxylic acid diethyl ester prepared in this way.

[0156] NMR spectroscopy: 1 H-NMR (500MHz, CDCl3): δ1.18(s,6H),1.23(t,J=7.3Hz,3H),1.28(t,J=7.3Hz,3H),2.35(s,2H ),4.10(q,J=7.3Hz,2H),4.18(q,J=7.3Hz,2H),5.76(d,J=16.1Hz,1H),7.00(d,J=16.1Hz,1H); 13 C-NMR (75.6MHz, CDCl3): δ14.19, 14.21, 26.53 (2C), 35.99, 46.17, 60.23, 60.29, 118.11, 156.06, 166.89, 170.95.

[0157] Mass spectrum: EI-mass spectrum (70eV): m / z 228 (M + ),213,199,183,167,154,141,126,109,95,81,67,55,41,29.

[0158] Infrared absorption spectrum (NaCl): νmax 2980, 2875, 1731, 1650, 1466, 1368, 1305, 1178, 1035, 982, 864, 722.

[0159] Example 4: Preparation of (E) 5-ethoxycarbonyl-4,4-dimethyl-2-pentenoic acid tert-butyl ester (8:R 1 =Et, R 2 = t Bu;1:R 1 =Et, R 2 = t Bu, R 3 =H)

[0160]

[0161] int Bu represents a tert-butyl group, and Et represents an ethyl group.

[0162] A solution of 0.00476 mol / g sodium acetylide in xylene (43.5 g, 0.207 mol) and THF (270 g) were placed in a reactor and cooled to 4 to 6° C. while stirring. Then, tert-butyl diethylphosphonoacetate (3:R 2 = t Bu; R 3 =H; R 4 =Et) (46.4 g, 0.207 mol). After the addition was completed, the mixture was heated to 62° C. to 67° C., and then ethyl 3,3-dimethyl-4-oxobutyrate (4:R 1 =Et) (28.5 g, 0.180 mol). After the dropwise addition was completed, the mixture was stirred at 62°C to 67°C for 5 hours. The mixture was then cooled to 4°C to 6°C, and an aqueous solution of ammonium chloride (190 g:

[0163] The obtained organic layer was washed with aqueous ammonium chloride solution (294 g: prepared from ammonium chloride (17 g), sodium chloride (7 g) and water (270 g)), and then washed with brine (284 g: prepared from sodium chloride (14 g) and water (270 g)). The organic layer was concentrated under reduced pressure, and the concentrate was distilled under reduced pressure to obtain (E) 5-ethoxycarbonyl-4,4-dimethyl-2-pentenoic acid tert-butyl ester (8: R 1 =Et; R 2 = t Bu) (29.4 g, 0.115 mol), the yield was 63.7%.

[0164] The following is the (E) tert-butyl 5-ethoxycarbonyl-4,4-dimethyl-2-pentenoate (8:R 1 =Et; R 2 = t Bu).

[0165] NMR spectroscopy: 1 H-NMR (500MHz, CDCl3): δ1.16 (s, 6H), 1.21 (t, J = 7.3Hz, 3H), 1.46 (s, 9H), 2.32 (s,2H),4.08(q,J=7.3Hz,2H),5.66(d,J=15.7Hz,1H),6.87(d,J=15.7Hz,1H); 13C-NMR (75.6MHz, CDCl3): δ14.17, 26.55 (2C), 28.09 (3C), 35.83, 46.17, 60.14, 80.14, 119.72, 154.82, 166.19, 170.97.

[0166] Mass spectrum: EI-mass spectrum (70eV): m / z 256 (M + ),200,183,169,154,137,113,95,81,57,41,27.

[0167] Infrared absorption spectrum (NaCl): νmax 2977,1734,1715,1651,1466,1392,1368,1318,1152,1036,977,865,768,723.

[0168] Example 5: Preparation of ethyl 3,5,5-trimethyl-2-oxo-3-cyclopentene-1-carboxylate (6:R 1 =Et;2:R 1 =Et, R 3 =Me)

[0169]

[0170] wherein Et represents an ethyl group.

[0171] Potassium tert-butoxide (231 g, 2.00 mol), toluene (1,000 g) and THF (500 g) were placed in a reactor and stirred at room temperature for 20 minutes. Next, diethyl 1,3,3-trimethyl-1-butene-1,4-dicarboxylate (5:R) obtained according to the procedure described in Example 2 was added dropwise at 40°C or below. 1 =R 2 =Et) (242g, 1.00mol; Z / E=33:67). After completion of the dropwise addition, the mixture was stirred at 65°C to 70°C for 2 hours and cooled to 4°C to 10°C. Then, 3.34 wt% hydrochloric acid (2,296g) was added to quench the reaction, and the resulting reaction mixture was phase separated. Then, the resulting organic layer was washed twice with water (2,000g), and then washed with brine (2,200g: prepared from sodium chloride (200g) and water (2,000g)). The resulting organic layer was concentrated under reduced pressure, and the concentrate was distilled under reduced pressure to obtain ethyl 3,5,5-trimethyl-2-oxo-3-cyclopentene-1-carboxylate (6:R 1 =Et) (171 g, 0.871 mol), the yield was 87.1%.

[0172] The following is the 3,5,5-trimethyl-2-oxo-3-cyclopentene-1-carboxylic acid ethyl ester (6:R 1 =Et) spectral data.

[0173] NMR spectroscopy: 1 H-NMR (500MHz, CDCl3): δ1.15 (s, 3H), 1.27 (t, J = 7.3Hz, 3H), 1.31 (s, 3H), 1.7 6(d,J=1.6Hz,3H),3.14(s,1H),4.19(q,J=7.3Hz,2H),7.04(q,J=1.6Hz,1H); 13 C-NMR (75.6MHz, CDCl3): δ9.86,14.22,23.90,29.15,42.44,60.93,62.67,138.34,166.33,169.22,203.61.

[0174] Mass spectrum: EI-mass spectrum (70eV): m / z 196 (M + ),181,168,151,135,123,109,95,79,67,55,39,29.

[0175] Infrared absorption spectrum (NaCl): νmax 2965, 2928, 2872, 1741, 1708, 1644, 1563, 1465, 1447, 1367, 1312, 1149, 1030, 997, 953, 898, 641, 529.

[0176] Example 6: Preparation of 5,5-dimethyl-2-oxo-3-cyclopentene-1-carboxylic acid ethyl ester (9:R 1 =Et;2:R 1 =Et, R 3 =H)

[0177]

[0178] wherein Et represents an ethyl group.

[0179] Potassium tert-butoxide (18.2 g, 0.162 mol), toluene (80.9 g) and THF (40.5 g) were placed in a reactor and stirred at room temperature for 10 minutes. Next, 3,3-dimethyl-1-butene-1,4-dicarboxylic acid diethyl ester (8:R) obtained by further distilling a portion of 3,3-dimethyl-1-butene-1,4-dicarboxylic acid diethyl ester obtained according to the procedure described in Example 3 was added dropwise at 35° C. or below. 1 =R 2=Et) (18.5 g, 0.0809 mol; Z / E=81:19). After the addition was completed, the mixture was stirred at room temperature for 30 minutes and cooled to 4°C to 10°C. Then, 3.34% by weight of hydrochloric acid (186 g) was added to quench the reaction, and the resulting reaction mixture was phase separated. Then, the resulting organic layer was washed twice with water (150 g) and then with saturated brine (150 mL). The resulting organic layer was concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (eluent: gradient of n-hexane: ethyl acetate = 20:1 to 4:1) to obtain the target compound 5,5-dimethyl-2-oxo-3-cyclopentene-1-carboxylic acid ethyl ester (9:R 1 =Et) (10.4 g, 0.0573 mol), the yield was 70.8%, and the by-product 3,3-dimethyl-5-oxo-1-cyclopentene-1-carboxylic acid ethyl ester (11: R 1 =Et) (1.27 g, 0.00698 mol), the yield was 8.6%.

[0180] The following is the ethyl 5,5-dimethyl-2-oxo-3-cyclopentene-1-carboxylate (9:R 1 =Et) spectral data.

[0181] NMR spectroscopy: 1 H-NMR (500MHz, CDCl3): δ1.19 (s, 3H), 1.26 (t, J = 7.3Hz, 3H), 1.35 (s, 3H), 3.1 2(s,1H),4.19(q,J=7.3Hz,2H),6.05(d,J=5.8Hz,1H),7.43(d,J=5.8Hz,1H); 13 C-NMR (75.6MHz, CDCl3): δ14.17, 23.59, 28.86, 45.03, 61.04, 62.48, 130.37, 168.89, 172.50, 203.65.

[0182] In the NMR spectrum, peaks corresponding to the enol form (keto-enol tautomer) of ethyl 5,5-dimethyl-2-oxo-3-cyclopentene-1-carboxylate were partially observed. This spectrum is for the keto form of ethyl 5,5-dimethyl-2-oxo-3-cyclopentene-1-carboxylate, but some peaks of the enol form (i.e., keto-enol tautomer) can also be seen.

[0183] Mass spectrum: EI-mass spectrum (70eV): m / z 182 (M + ),167,154,137,121,109,95,81,65,53,39,29.

[0184] Infrared absorption spectrum (NaCl): νmax 3400,2968,2938,2874,1742,1707,1594,1469,1368,1316,1252,1229,1145,1036,917,814,754,694,517.

[0185] Some absorption of the enol form of ethyl 5,5-dimethyl-2-oxo-3-cyclopentene-1-carboxylate can also be seen in the infrared absorption spectrum.

[0186] The following is the 3,3-dimethyl-5-oxo-1-cyclopentene-1-carboxylic acid ethyl ester (11:R 1 =Et) spectral data.

[0187] NMR spectroscopy: 1 H-NMR (500MHz, CDCl3): δ1.26 (s, 6H), 1.32 (t, J = 7.3Hz, 3H), 2.39 (s, 2H), 4.27 (q, J = 7.3Hz, 2H), 8.08 (s, 1H); 13 C-NMR (75.6MHz, CDCl3): δ14.12, 27.42 (2C), 38.82, 51.12, 60.94, 134.03, 161.87, 179.68, 202.47.

[0188] Mass spectrum: EI-mass spectrum (70eV): m / z 182 (M + ),167,154,136,121,110,95,80,69,53,41,29.

[0189] Infrared absorption spectrum (NaCl): νmax 2963,2871,1751,1722,1621,1466,1411,1368,1333,1301,1232,1214,1192,1034,928,767,725,592.

Claims

1. A method for preparing a compound of the following general formula (2): Where R 1 represents a monovalent hydrocarbon group having 1 to 10 carbon atoms, and R 3 represents a hydrogen atom or a methyl group, The method comprises: The following compound of general formula (1): Where R 1 represents a monovalent hydrocarbon group having 1 to 10 carbon atoms, R 2 represents a monovalent hydrocarbon group having 1 to 10 carbon atoms, R 3 As defined above, and the wavy bond represents the E-configuration, the Z-configuration or a mixture thereof, The compound (2) is formed by a Dieckmann condensation reaction in the presence of a base, and the base is sodium tert-butoxide or potassium tert-butoxide.

2. The method for preparing compound (2) according to claim 1, wherein R in the general formula (1) 1 and R 2 represents an ethyl group, and R 3 Represents a methyl group.

3. The method for preparing compound (2) according to claim 1, further comprising: The phosphonate anion is generated from the phosphonate compound of the following general formula (3): Where R 2 and R 3 As defined in claim 1, and R 4 represents a monovalent hydrocarbon group or a halogenated alkyl group having 1 to 10 carbon atoms, A Horner-Wordsworth-Emmons reaction is carried out with an aldehyde compound of the following general formula (4): Where R 1 As defined in claim 1, To form the compound (1).

4. The method for preparing compound (2) according to claim 3, wherein R in the general formula (3) 2 and R 4 is an ethyl group, and R 3 It is a methyl group.

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