Process for the preparation of 2-(1,5,5-trimethyl-2-cyclopentenyl)ethyl acetate

Abstract

The present invention provides a method for preparing 2-(1,5,5-trimethyl-2-cyclopentenyl)ethyl acetate of the following general formula (3), wherein Ac represents an acetyl group, the method comprising: subjecting a haloacetaldehyde alkyl 3,4,4-trimethyl-2-cyclopentenyl acetal compound of the following general formula (1), wherein R represents a linear or branched alkyl group having 1 to 4 carbon atoms, and Y represents a halogen atom, to a dehydrohalogenation reaction in the presence of a base, followed by a rearrangement reaction to obtain a (1,5,5-trimethyl-2-cyclopentenyl)acetate compound of the following general formula (2), wherein R is as defined above, and subjecting the alkoxycarbonylmethyl group of the (1,5,5-trimethyl-2-cyclopentenyl)acetate compound (2) to a multi-step conversion to convert to a 2-acetyloxyethyl group, thereby obtaining 2-(1,5,5-trimethyl-2-cyclopentenyl)-ethyl acetate (3).

Description

Technical Field

[0001] This invention relates to a method for preparing ethyl 2-(1,5,5-trimethyl-2-cyclopentenyl)acetate. Background Technology

[0002] The long-tailed mealybug (scientific name: *Pseudococcus longispinus*) is a pest belonging to the order Hemiptera and the family Pseudococcidae. It sucks the sap from many agricultural plants, such as grapes, apples, citrus fruits, and pears, damaging these plants. Furthermore, the long-tailed mealybug secretes honeydew, which contains sugar and can lead to fungal diseases. These damages and diseases reduce the yield and quality of these agricultural plants, posing a serious problem.

[0003] Insecticides are commonly used to control mealybugs. However, mealybugs live in narrow spaces within leaves and / or plant bark, and are covered in a waxy substance. Therefore, insecticides have difficulty coming into contact with the pests' bodies, resulting in insufficient effectiveness.

[0004] Given the adverse environmental and human health effects of pesticides, there is a recent demand for the development of new, highly safe, and eco-friendly control methods, such as mating disruption and / or large-scale trapping using insect sex pheromones. Developing such new control methods requires the large-scale, inexpensive industrial production of sex pheromones.

[0005] It has been reported that the sex pheromone of the mealybug is optically active ethyl (-)-2-(1,5,5-trimethyl-2-cyclopentenyl)acetate (Non-Patent Literature 1 listed below). Furthermore, it has been reported that there is no difference in the attraction activity of ethyl (-)-2-(1,5,5-trimethyl-2-cyclopentenyl)acetate as a sex pheromone and racemic (±)-2-(1,5,5-trimethyl-2-cyclopentenyl)acetate as an enantiomeric equivalent mixture for the mealybug (Non-Patent Literature 1). Therefore, considering the inexpensive supply of pheromones and economical control methods, finding a method for preparing racemic (±)-2-(1,5,5-trimethyl-2-cyclopentenyl)acetate is effective in establishing a technology for pest control using sex pheromones.

[0006] The following is a method for preparing this racemic pheromone. 3,4,4-Trimethyl-2-cyclopenten-1-ol is acetylated, and the reaction product is then reacted with a base, followed by a reaction with tert-butyldimethylchlorosilane, causing the reaction product to undergo an Ireland-Claisen rearrangement to form (1,5,5-trimethyl-2-cyclopentenyl)acetic acid as an intermediate. The functional groups of the intermediate are then converted to those of the target compound (Non-Patent Literature 2 listed below).

[0007] Similar to the aforementioned Eland-Claisen rearrangement, the Johnson-Claisen rearrangement is referred to as a Claisen-type rearrangement of allyl alcohols (such as 2-cyclopenten-1-ol compounds), in which 2-cyclopenten-1-ol compounds react with trialkyl orthoacetate in the presence of a weakly acidic catalyst (such as propionic acid) to form (2-cyclopentenyl)acetate compounds (Non-Patent Literature 3 listed below).

[0008] List of Literature

[0009] [Non-patent literature]

[0010] [Non-patent literature 1] R. Ramesh et al., J. Org. Chem., 2015, 80, 7785-7789

[0011] [Non-Patent Literature 2] JGMillar et al., Synlett, 15(2010) 2319-2321

[0012] [Non-Patent Literature 3] W.S. Johnson et al., J. Am. Chem. Soc., 92 (1970), 92, 741-743

[0013] The problem to be solved by this invention

[0014] However, the preparation method using the Elland-Claisen rearrangement reaction described in Non-Patent Literature 2 has the disadvantages of using flammable organolithium compounds and lithium amines; the reaction must be carried out at extremely low temperatures (e.g., -78°C); and the use of industrially relatively expensive trialkylchlorosilanes.

[0015] In the method for preparing (2-cyclopentenyl)acetic acid ester compounds via the Johnson-Clayson rearrangement reaction described in Non-Patent Literature 3 (wherein the 2-cyclopenten-1-ol compound reacts with a trialkyl orthoacetate in the presence of a weakly acidic catalyst), the dehydration reaction of the starting material 2-cyclopenten-1-ol compound occurs preferentially, leading to a problematic low yield (see Non-Patent Literature 2 and Comparative Example 1 described in this specification). Therefore, the prior art cannot economically and industrially produce (1,5,5-trimethyl-2-cyclopentenyl)acetic acid and (1,5,5-trimethyl-2-cyclopentenyl)acetic acid ester compounds as intermediates in large quantities. Summary of the Invention

[0016] The present invention was made under these circumstances with the aim of overcoming the aforementioned problems of the prior art and providing an industrial and economical method for preparing ethyl 2-(1,5,5-trimethyl-2-cyclopentenyl)acetate.

[0017] As a result of in-depth research, the inventors now provide a novel alkyl 3,4,4-trimethyl-2-cyclopentenyl acetal compound, and have discovered that (1,5,5-trimethyl-2-cyclopentenyl) acetate compounds can be prepared by subjecting the alkyl 3,4,4-trimethyl-2-cyclopentenyl acetal compound to dehydrohalogenation in the presence of a base, followed by a rearrangement reaction, within an industrially readily applicable reaction temperature range, without the use of flammable and industrially expensive starting materials.

[0018] The inventors have also discovered that ethyl 2-(1,5,5-trimethyl-2-cyclopentenyl)acetate can be prepared efficiently and industrially by subjecting the alkoxycarbonyl methyl group (i.e., -CH2C(=O)OR) of the (1,5,5-trimethyl-2-cyclopentenyl)acetate compound thus prepared to a 2-acetoxyethyl group (i.e., -CH2CH2OAc) through a multi-step transformation, thereby completing the present invention.

[0019] According to one aspect of the present invention, the present invention provides a method for preparing ethyl 2-(1,5,5-trimethyl-2-cyclopentenyl)acetate (3) of formula (3):

[0020]

[0021] Where Ac represents the acetyl group.

[0022] The method includes:

[0023] The following haloacetal alkyl 3,4,4-trimethyl-2-cyclopentenyl acetals of general formula (1) are subjected to dehydrohalogenation in the presence of a base:

[0024]

[0025] Where R represents a straight-chain or branched alkyl group having 1 to 4 carbon atoms, and Y represents a halogen atom.

[0026] A rearrangement reaction was then carried out to obtain a (1,5,5-trimethyl-2-cyclopentenyl) acetate compound of the following general formula (2):

[0027]

[0028] Where R is defined above, and

[0029] The alkoxycarbonyl methyl group (i.e., -CH2C(=O)OR) of (1,5,5-trimethyl-2-cyclopentenyl)acetate compound (2) is subjected to a multi-step transformation to convert to a 2-acetoxyethyl group (i.e., -CH2CH2OAc), thereby obtaining 2-(1,5,5-trimethyl-2-cyclopentenyl)acetate (3).

[0030] According to the present invention, (1,5,5-trimethyl-2-cyclopentenyl)acetate compound (2) can be prepared within an industrially readily applicable reaction temperature range without the use of flammable and industrially expensive starting materials. Ethyl 2-(1,5,5-trimethyl-2-cyclopentenyl)acetate compound (2) obtained therefrom can be industrially and economically prepared by subjecting the alkoxycarbonylmethyl group (i.e., -CH2C(=O)OR) of the resulting compound (2) to a multi-step conversion to a 2-acetoxyethyl group (i.e., -CH2CH2OAc). Detailed Implementation

[0031] The embodiments of the present invention will now be described in detail. It should be noted that the present invention is not limited to these embodiments, nor is it restricted by them.

[0032] A. The following describes a novel compound of general formula (1), a haloacetal alkyl 3,4,4-trimethyl-2-cyclopentenyl acetal.

[0033]

[0034] In general formula (1), R represents a straight-chain or branched alkyl group having 1 to 4 carbon atoms, and Y represents a halogen atom.

[0035] Examples of alkyl groups include straight-chain alkyl groups, such as methyl, ethyl, n-propyl, and n-butyl groups; and branched-chain alkyl groups, such as isopropyl and isobutyl groups. Methyl, ethyl, and n-propyl groups are preferred for reactivity and / or yield.

[0036] Examples of halogen atoms include chlorine, bromine, and iodine atoms. Bromine or iodine atoms are preferred considering reactivity and / or yield.

[0037] Examples of alkyl 3,4,4-trimethyl-2-cyclopentenyl acetals (1) include the following compounds:

[0038] Chloroacetaldehyde straight-chain alkyl 3,4,4-trimethyl-2-cyclopentenyl acetals, such as chloroacetaldehyde methyl 3,4,4-trimethyl-2-cyclopentenyl acetal, chloroacetaldehyde ethyl 3,4,4-trimethyl-2-cyclopentenyl acetal, chloroacetaldehyde n-propyl 3,4,4-trimethyl-2-cyclopentenyl acetal, and chloroacetaldehyde n-butyl 3,4,4-trimethyl-2-cyclopentenyl acetal;

[0039] Bromoacetaldehyde straight-chain alkyl 3,4,4-trimethyl-2-cyclopentenyl acetals, such as bromoacetaldehyde methyl 3,4,4-trimethyl-2-cyclopentenyl acetal, bromoacetaldehyde ethyl 3,4,4-trimethyl-2-cyclopentenyl acetal, bromoacetaldehyde n-propyl 3,4,4-trimethyl-2-cyclopentenyl acetal and bromoacetaldehyde n-butyl 3,4,4-trimethyl-2-cyclopentenyl acetal;

[0040] Iodoacetaldehyde straight-chain alkyl 3,4,4-trimethyl-2-cyclopentenyl acetals, such as iodoacetaldehyde methyl 3,4,4-trimethyl-2-cyclopentenyl acetal, iodoacetaldehyde ethyl 3,4,4-trimethyl-2-cyclopentenyl acetal, iodoacetaldehyde n-propyl 3,4,4-trimethyl-2-cyclopentenyl acetal, and iodoacetaldehyde n-butyl 3,4,4-trimethyl-2-cyclopentenyl acetal;

[0041] Chloroacetaldehyde branched alkyl 3,4,4-trimethyl-2-cyclopentenyl acetals, such as chloroacetaldehyde isopropyl 3,4,4-trimethyl-2-cyclopentenyl acetal and chloroacetaldehyde isobutyl 3,4,4-trimethyl-2-cyclopentenyl acetal.

[0042] Bromoacetaldehyde branched alkyl 3,4,4-trimethyl-2-cyclopentenyl acetals, such as bromoacetaldehyde isopropyl 3,4,4-trimethyl-2-cyclopentenyl acetal and bromoacetaldehyde isobutyl 3,4,4-trimethyl-2-cyclopentenyl acetal; and

[0043] Iodoacetaldehyde branched alkyl 3,4,4-trimethyl-2-cyclopentenyl acetals, such as iodoacetaldehyde isopropyl 3,4,4-trimethyl-2-cyclopentenyl acetal and iodoacetaldehyde isobutyl 3,4,4-trimethyl-2-cyclopentenyl acetal.

[0044] Specifically, considering reactivity, the alkyl 3,4,4-trimethyl-2-cyclopentenyl acetal compound (1) is preferably a straight-chain alkyl 3,4,4-trimethyl-2-cyclopentenyl acetal compound of bromoacetaldehyde and a straight-chain alkyl 3,4,4-trimethyl-2-cyclopentenyl acetal compound of iodoacetaldehyde.

[0045] Furthermore, the alkyl 3,4,4-trimethyl-2-cyclopentenyl acetal compound (1) can be its enantiomers, diastereomers, and mixtures of the same or different amounts of such stereoisomers.

[0046] Next, the method for preparing the alkyl 3,4,4-trimethyl-2-cyclopentenyl acetal compound (1) will be described below.

[0047] The alkyl 3,4,4-trimethyl-2-cyclopentenyl acetal compound (1) can be prepared, for example, by halogenating an alkyl vinyl ether compound of the following general formula (7) with a halogenating agent to form a halide, and then subjecting the resulting halide to a substitution reaction with 3,4,4-trimethyl-2-cyclopenten-1-ol of the following general formula (8), as shown in the following reaction formula.

[0048]

[0049] The method for preparing the alkyl 3,4,4-trimethyl-2-cyclopentenyl acetal compound (1) will be described in further detail below.

[0050] The alkyl vinyl ether compounds (7) used as starting materials will be described below.

[0051] R in general formula (7) is defined as in general formula (1).

[0052] Examples of alkyl vinyl ether compounds (7) include linear alkyl vinyl ethers such as methyl vinyl ether, ethyl vinyl ether, n-propyl vinyl ether and n-butyl vinyl ether, and branched alkyl vinyl ethers such as isopropyl vinyl ether and isobutyl vinyl ether.

[0053] Alkyl vinyl ether compounds (7) can be purchased on the market or prepared at home.

[0054] Halogenation of alkyl vinyl ether compounds (7) can be carried out using halogenating agents, and may be carried out by heating or cooling if necessary.

[0055] Examples of halogenating agents used in halogenation include chlorinating agents such as chlorine, thioyl chloride, N-chlorosuccinimide, dichloroiodobenzene, tetrabutyl iodotetrachloride, titanium tetrachloride (IV), and copper chloride (II); brominating agents such as bromine, N-bromosuccinimide, N-bromoacetamide, 1,3-dibromo-5,5-dimethylhydantoin, tetrabutyltribromide, phenyltrimethyltribromide, dibromoiodobenzene, copper bromide (II), cuprous bromide (I), magnesium bromide (II), and aluminum bromide; iodizing agents such as iodine, N-iodosuccinimide, and 1,3-diiodo-5,5-dimethylhydantoin; and chloroiodizing agents such as iodine monochloride and potassium tetrachloroiodate. Brominating agents and iodizing agents are preferred. Considering reactivity and / or yield, bromine and N-bromosuccinimide in the brominating agent and iodine and N-iodosuccinimide in the iodizing agent are preferred.

[0056] The amount of halogenating agent used in halogenation varies depending on the structure and / or reactivity of the alkyl vinyl ether compound (7) and / or the reducing agent. Considering the yield and / or the generation of impurities as byproducts, the amount is preferably 0.2 mol to 5.0 mol, more preferably 0.5 mol to 2.0 mol, relative to each mol of alkyl vinyl ether compound (7).

[0057] The solvent used in halogenation can be any solvent that does not adversely affect the halogenation process. Examples of solvents used in halogenation include halogen-based solvents such as dichloromethane, chloroform, carbon tetrachloride, and 1,2-dichloroethane; ether solvents such as diethyl ether, di-n-butyl ether, di-tert-butyl ether, tetrahydrofuran, 1,4-dioxane, and diethylene glycol dimethyl ether; hydrocarbon solvents such as hexane and heptane; and aprotic polar solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, and hexamethylphosphoric triamine. Halogen-based solvents, ether solvents, and aprotic polar solvents are preferred considering reactivity.

[0058] If necessary, the solvent may be used alone or in combination thereof, and may optionally be determined while taking into account the type and / or reactivity and / or selectivity of the alkyl vinyl ether compound (7) and / or the halogenating agent.

[0059] While taking into account the type and / or reactivity of the alkyl vinyl ether compound (7) and / or the halogenating agent, the amount of solvent used in halogenation may optionally be determined, for example, taking into account reactivity and / or the formation of impurities as byproducts, the amount of solvent is preferably 50 g to 10,000 g, more preferably 500 g to 8,000 g, relative to each mol of the alkyl vinyl ether compound (7).

[0060] While taking into account the reactivity of the alkyl vinyl ether compound (7) and / or the formation of halogenating agents and / or impurities, the halogenation reaction temperature may optionally be determined, for example, preferably -60°C to 150°C, more preferably -20°C to 50°C, taking into account the reactivity and / or the formation of impurities.

[0061] Preferably, the halogenation reaction time is optimized based on the reactivity of the alkyl vinyl ether compound (7) and / or the halogenating agent by monitoring the reaction progress using, for example, gas chromatography and / or thin-layer chromatography to confirm the disappearance of the alkyl vinyl ether compound (7) and / or the halogenating agent. For example, taking into account yield and / or the formation of impurities, the halogenation reaction time is preferably 0.5 hours to 168 hours, more preferably 0.5 hours to 24 hours, and even more preferably 0.5 hours to 6 hours.

[0062] Halides prepared by halogenating alkyl vinyl ether compounds (7) with a halogenating agent are considered to be alkyl 1,2-dihaloethyl ethers having the following general formula (9). The halides may be isolated and / or purified after halogenation and then used in subsequent steps, or may be used as is in the reaction mixture in subsequent steps without isolation and / or purification after halogenation.

[0063]

[0064] In general formula (9), R is as defined in general formula (7), and Y represents halogen atoms independently of each other. Examples of halogen atoms include chlorine, bromine, and iodine atoms. Bromine or iodine atoms are preferred for yield and / or reactivity. Y can be the same or different independently of each other. For example, when the halogenating agent is a chloroiodizing agent (such as iodine monochloride or potassium tetrachloroiodate), Y can be different independently of each other.

[0065] Next, 3,4,4-trimethyl-2-cyclopenten-1-ol (8) can be commercially available or prepared in-house.

[0066] In the substitution reaction, the halogen atom (i.e., secondary Y) in the halide is replaced by 3,4,4-trimethyl-2-cyclopenten-1-ol (8) to form a haloacetal alkyl 3,4,4-trimethyl-2-cyclopentenyl acetal compound (1).

[0067] Considering yield and / or byproduct formation and / or economy, the amount of 3,4,4-trimethyl-2-cyclopenten-1-ol (8) used is preferably 0.2 mol to 5.0 mol, more preferably 0.5 mol to 2.0 mol, relative to each mol of alkyl vinyl ether compound (7).

[0068] If necessary, the substitution reaction can be carried out by heating or cooling. Considering the reactivity of 3,4,4-trimethyl-2-cyclopenten-1-ol (8) and halides and / or the formation of impurities as byproducts, the substitution reaction can be carried out in the presence of a base.

[0069] Examples of bases include amines such as triethylamine, diisopropylethylamine, pyridine, N,N-dimethylaminopyridine, and N,N-dimethylaniline; organometallic compounds such as n-butyllithium, methyllithium, and phenyllithium; metal amides such as diisopropylaminolithium, hexamethyldisilaminolithium, hexamethyldisilaminosodium, and dicyclohexylaminolithium; metal hydroxides such as sodium hydroxide and potassium hydroxide; and metal carbonates such as potassium carbonate, sodium carbonate, and sodium bicarbonate.

[0070] If necessary, the base may be used alone or in combination with it, and may optionally be determined while taking into account the reactivity of 3,4,4-trimethyl-2-cyclopenten-1-ol (8) and / or the formation of halides and / or impurities.

[0071] The amount of base used may be optionally determined while taking into account the reactivity of 3,4,4-trimethyl-2-cyclopenten-1-ol (8) and / or the formation of halides and / or impurities. For example, the amount is preferably 0.5 mol to 5.0 mol, more preferably 0.8 mol to 2.0 mol, relative to each mol of 3,4,4-trimethyl-2-cyclopenten-1-ol (8), taking into account reactivity and / or economy.

[0072] The solvent used in a substitution reaction can be any solvent that does not adversely affect the substitution reaction. Examples of solvents used in substitution reactions include halogen-based solvents such as dichloromethane, chloroform, carbon tetrachloride, and 1,2-dichloroethane; hydrocarbon solvents such as hexane, heptane, benzene, and toluene; ether solvents such as diethyl ether, tetrahydrofuran, 1,4-dioxane, and diethylene glycol dimethyl ether; nitrile solvents such as acetonitrile; ketone solvents such as acetone, methyl ethyl ketone, and diisobutyl ketone; ester solvents such as ethyl acetate and butyl acetate; and aprotic polar solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, and hexamethylphosphoric triamine. Halogen-based solvents, ether solvents, and aprotic polar solvents are preferred, considering reactivity and / or yield.

[0073] If necessary, the solvent may be used alone or in combination, and may optionally be determined while taking into account the type and / or reactivity and / or selectivity of 3,4,4-trimethyl-2-cyclopenten-1-ol (8) and / or the halide.

[0074] The solvent used in the substitution reaction can be the same solvent that was used in the halogenation as before. Any solvent of the same type as that used in the halogenation or any solvent different from that used in the halogenation can be added to the substitution reaction system to increase reactivity and / or adjust the concentration.

[0075] The amount of solvent used in the substitution reaction may be optionally determined while taking into account the reactivity of 3,4,4-trimethyl-2-cyclopenten-1-ol (8) and / or the formation of halides and / or impurities. For example, taking into account the reactivity and / or the formation of impurities as byproducts, the amount is preferably 50 g to 10,000 g, more preferably 500 g to 8,000 g, relative to each mol of 3,4,4-trimethyl-2-cyclopenten-1-ol (8).

[0076] While taking into account the reactivity of 3,4,4-trimethyl-2-cyclopenten-1-ol (8) and / or the formation of halides and / or impurities, the reaction temperature of the substitution reaction may optionally be determined, for example, preferably -60°C to 150°C, more preferably -20°C to 50°C, taking into account the reactivity and / or the formation of impurities.

[0077] Preferably, the reaction time of the substitution reaction is optimized based on the reactivity of 3,4,4-trimethyl-2-cyclopenten-1-ol (8) and / or the halide by monitoring the reaction progress using, for example, gas chromatography and / or thin-layer chromatography to confirm the disappearance of 3,4,4-trimethyl-2-cyclopenten-1-ol (8) and / or the halide. For example, taking into account yield and / or impurity formation, the reaction time of the substitution reaction is preferably from 1 hour to 168 hours, more preferably from 1 hour to 24 hours, and even more preferably from 1 hour to 6 hours.

[0078] The alkyl 3,4,4-trimethyl-2-cyclopentenyl acetal compound (1) formed in the substitution reaction can be appropriately separated and / or purified by any purification method commonly used in organic synthesis, such as vacuum distillation and / or various chromatographic methods. Vacuum distillation is preferred for industrial economics. When the alkyl 3,4,4-trimethyl-2-cyclopentenyl acetal compound (1) formed in the substitution reaction has sufficient purity, the crude product containing the alkyl 3,4,4-trimethyl-2-cyclopentenyl acetal compound (1) can be used directly in subsequent steps without purification.

[0079] B. Next, a method for preparing (1,5,5-trimethyl-2-cyclopentenyl) acetate compounds of the following general formula (2) will be described below.

[0080] (1,5,5-trimethyl-2-cyclopentenyl)acetate compound (2) was prepared by dehydrohalogenation (-HY) of haloacetaldehyde alkyl 3,4,4-trimethyl-2-cyclopentenyl acetal compound (1) in the presence of a base, followed by a rearrangement reaction, as shown in the following reaction formula (see Examples 1-1 to 1-6 below).

[0081]

[0082] The starting material is a haloacetal alkyl 3,4,4-trimethyl-2-cyclopentenyl acetal compound (1) as described above. R in general formula (1) is as defined above, and considering reactivity, a straight-chain alkyl group having 1 to 4 carbon atoms is preferred. Considering reactivity and / or availability, a straight-chain alkyl group having 1 to 3 carbon atoms, i.e., a methyl group, an ethyl group, and a n-propyl group, is more preferred.

[0083] Next, the (1,5,5-trimethyl-2-cyclopentenyl) acetate compound (2) to be formed in the rearrangement reaction will be described below.

[0084] R in general formula (2) is defined as in general formula (1).

[0085] Examples of (1,5,5-trimethyl-2-cyclopentenyl) acetate compounds (2) include straight-chain alkyl (1,5,5-trimethyl-2-cyclopentenyl) acetate compounds, such as methyl (1,5,5-trimethyl-2-cyclopentenyl) acetate, ethyl (1,5,5-trimethyl-2-cyclopentenyl) acetate, n-propyl (1,5,5-trimethyl-2-cyclopentenyl) acetate and n-butyl (1,5,5-trimethyl-2-cyclopentenyl) acetate; and branched-chain alkyl (1,5,5-trimethyl-2-cyclopentenyl) acetate compounds, such as isopropyl (1,5,5-trimethyl-2-cyclopentenyl) acetate and isobutyl (1,5,5-trimethyl-2-cyclopentenyl) acetate.

[0086] Furthermore, when R in general formula (2) does not have any asymmetric carbon atoms, the (1,5,5-trimethyl-2-cyclopentenyl)acetate compound (2) includes (R)(1,5,5-trimethyl-2-cyclopentenyl)acetate compound, (S)(1,5,5-trimethyl-2-cyclopentenyl)acetate compound, and their racemic and scalemic mixtures. On the other hand, when R in general formula (2) has one or more asymmetric carbon atoms, the (1,5,5-trimethyl-2-cyclopentenyl)acetate compound (2) can be its enantiomers, diastereomers, and mixtures of the same or different amounts of such stereoisomers.

[0087] Dehydrohalogenation reactions can be carried out in the presence of a base, and can be performed by heating or cooling if necessary.

[0088] Examples of bases used in dehydrohalogenation reactions include metal alkoxides such as sodium methoxide, sodium ethoxide, sodium tert-butoxide, lithium methoxide, lithium ethoxide, lithium tert-butoxide, potassium methoxide, potassium ethoxide, and potassium tert-butoxide; metal hydroxides such as sodium hydroxide, lithium hydroxide, and potassium hydroxide; organometallic reagents such as methyllithium, ethyllithium, n-butyllithium, and methylmagnesium chloride; metal amines such as diisopropylaminolithium, hexamethyldisilaminolithium, hexamethyldisilaminosodium, and dicyclohexylaminolithium; and organonitrogen compounds such as triethylamine, diisopropylethylamine, tributylamine, N,N-dimethylaniline, pyridine, 4-dimethylaminopyridine, pyrrolidine, piperidine, trimethylpyridine, dimethylpyridine, morpholine, piperazine, 1,8-diazabicyclo[5.4.0]undec-7-ene, and 1,5-diazabicyclo[4.3.0]non-5-ene. Considering reactivity and / or the formation of impurities, metal alkoxides are preferred, and sodium tert-butoxide, lithium tert-butoxide, and potassium tert-butoxide are more preferred.

[0089] If necessary, the base may be used alone or in combination with it, and may optionally be determined while taking into account the type and / or reactivity and / or selectivity of the alkyl 3,4,4-trimethyl-2-cyclopentenyl acetal compound (1).

[0090] The amount of base used may vary depending on the structure and / or reactivity of the alkyl halogenated 3,4,4-trimethyl-2-cyclopentenyl acetal compound (1). For example, taking into account yield and / or the formation of impurities, the amount is preferably 0.2 mol to 5.0 mol, more preferably 0.5 mol to 2.0 mol, relative to each mol of the alkyl halogenated 3,4,4-trimethyl-2-cyclopentenyl acetal compound (1).

[0091] The solvent used in a dehydrohalogenation reaction can be any solvent that does not adversely affect the dehydrohalogenation reaction. Examples of solvents used in dehydrohalogenation reactions include alcohol solvents such as methanol, ethanol, isopropanol, and tert-butanol; ether solvents such as diethyl ether, di-n-butyl ether, di-tert-butyl ether, tetrahydrofuran, 1,4-dioxane, diethylene glycol dimethyl ether, and diethylene glycol diethyl ether; hydrocarbon solvents such as hexane, heptane, benzene, toluene, and xylene; aprotic polar solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, 1,3-dimethyl-2-imidazolinone, dimethyl sulfoxide, and hexamethylphosphoric triamine; and nitrile solvents such as acetonitrile. Ether solvents and aprotic polar solvents are preferred for reactivity, and N,N-dimethylformamide, N,N-dimethylacetamide, diethylene glycol dimethyl ether, and diethylene glycol diethyl ether are more preferred for reactivity.

[0092] If necessary, the solvent may be used alone or in combination, and may optionally be determined while taking into account the type and / or reactivity and / or selectivity of the alkyl 3,4,4-trimethyl-2-cyclopentenyl acetal compound (1).

[0093] The amount of solvent used may be optionally determined while taking into account the reactivity and / or solubility of the alkyl halogenated 3,4,4-trimethyl-2-cyclopentenyl acetal compound (1), for example, preferably 30 g to 10,000 g, more preferably 100 g to 5,000 g, relative to each mol of the alkyl halogenated 3,4,4-trimethyl-2-cyclopentenyl acetal compound (1), taking into account reactivity and / or economy.

[0094] While taking into account the reactivity of the alkyl 3,4,4-trimethyl-2-cyclopentenyl acetal compound (1) and / or the formation of impurities, the reaction temperature of the dehydrohalogenation reaction may optionally be determined, for example, preferably -60°C to 150°C, more preferably -20°C to 80°C, taking into account the reactivity and / or the formation of impurities.

[0095] Preferably, the reaction time of the dehydrohalogenation reaction is optimized based on the reactivity of the alkyl 3,4,4-trimethyl-2-cyclopentenyl acetal compound (1) as the substrate, by monitoring the reaction progress using, for example, gas chromatography and / or thin-layer chromatography to confirm the disappearance of the alkyl 3,4,4-trimethyl-2-cyclopentenyl acetal compound (1). For example, considering the yield and / or the formation of impurities, the reaction time of the dehydrohalogenation reaction is preferably from 1 hour to 168 hours, more preferably from 1 hour to 24 hours, and even more preferably from 1 hour to 12 hours.

[0096] During the dehydrohalogenation reaction, the alkyl 3,4,4-trimethyl-2-cyclopentenyl ketal compound of the following general formula (4) is considered to be formed in the reaction system as a product of the dehydrohalogenation reaction.

[0097]

[0098] R in general formula (4) is defined as in general formula (1).

[0099] The products of dehydrohalogenation reactions can be separated and / or purified using any purification method commonly used in organic synthesis (such as vacuum distillation and / or various chromatographic methods) and then used in subsequent rearrangement reactions. When the products of dehydrohalogenation reactions are difficult to separate and / or purify due to their properties, the products are preferably used as is in subsequent rearrangement reactions.

[0100] Next, in the rearrangement reaction, (1,5,5-trimethyl-2-cyclopentenyl)acetate compound (2) is prepared from the product of the dehydrohalogenation reaction via [3,3]-σ migration rearrangement, as shown in the following reaction formula. The carbon atom attached to the alkoxycarbonyl methyl group becomes quaternary, resulting in greater steric hindrance for (1,5,5-trimethyl-2-cyclopentenyl)acetate compound (2) and making it difficult to prepare (1,5,5-trimethyl-2-cyclopentenyl)acetate compound (2) using common anionic substances. Therefore, the preparation method using [3,3]-σ migration rearrangement is considered to be effective in the preparation of (1,5,5-trimethyl-2-cyclopentenyl)acetate compound (2).

[0101]

[0102] The rearrangement reaction can be carried out in a solvent or not, and can be carried out by heating or cooling if necessary.

[0103] The solvent used in a rearrangement reaction can be any solvent that does not adversely affect the rearrangement reaction. Examples of solvents used in rearrangement reactions include alcohol solvents such as methanol, ethanol, isopropanol, and tert-butanol; ether solvents such as diethyl ether, di-n-butyl ether, di-tert-butyl ether, tetrahydrofuran, 1,4-dioxane, and diethylene glycol dimethyl ether; hydrocarbon solvents such as hexane, heptane, benzene, toluene, and xylene; aprotic polar solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, 1,3-dimethyl-2-imidazolinone, dimethyl sulfoxide, and hexamethylphosphoric triamine; and nitrile solvents such as acetonitrile. Ether solvents and aprotic polar solvents are preferred considering reactivity.

[0104] If necessary, the solvent may be used alone or in combination, and may be optionally determined while taking into account the type and / or reactivity of the dehydrohalogenation reaction products.

[0105] When the products of a dehydrohalogenation reaction are used in a subsequent rearrangement reaction without separation and / or purification, the solvent used in the rearrangement reaction can be the same solvent used in the dehydrohalogenation reaction. Any additional solvent can be used in the rearrangement reaction system to adjust the reaction temperature and / or concentration.

[0106] The amount of solvent used in the rearrangement reaction can be optionally determined while taking into account the reactivity and / or solubility of the dehydrohalogenation product (the substrate of the rearrangement reaction). For example, considering reactivity and / or economy, the amount of solvent used relative to each mol of alkyl 3,4,4-trimethyl-2-cyclopentenyl acetal compound (1) or the product of the dehydrohalogenation reaction is preferably greater than 0 g to 10,000 g, more preferably 50 g to 3,000 g.

[0107] While taking into account the reactivity of the dehydrohalogenation reaction products and / or the formation of impurities, the reaction temperature of the rearrangement reaction can be optionally determined, for example, preferably -60°C to 250°C, more preferably 0°C to 150°C, and even more preferably 80°C to 120°C, taking into account the reactivity and / or the formation of impurities.

[0108] Preferably, the reaction time of the rearrangement reaction is optimized based on the reactivity of the dehydrohalogenation reaction products by monitoring the reaction progress using, for example, gas chromatography and / or thin-layer chromatography to confirm the disappearance of the dehydrohalogenation reaction products. For example, considering the yield and / or the formation of impurities, the reaction time of the rearrangement reaction is preferably 1 hour to 168 hours, more preferably 1 hour to 24 hours, and even more preferably 1 hour to 6 hours.

[0109] The (1,5,5-trimethyl-2-cyclopentenyl)acetate compound (2) formed in the rearrangement reaction can be appropriately separated and / or purified by any purification method commonly used in organic synthesis, such as vacuum distillation and / or various chromatographic methods. Vacuum distillation is preferred for industrial economics. When the (1,5,5-trimethyl-2-cyclopentenyl)acetate compound (2) formed in the rearrangement reaction has sufficient purity, the crude product containing the (1,5,5-trimethyl-2-cyclopentenyl)acetate compound (2) can be used directly in subsequent steps without purification.

[0110] C. The method for preparing ethyl 2-(1,5,5-trimethyl-2-cyclopentenyl) of formula (3) will be described below.

[0111] Ethyl 2-(1,5,5-trimethyl-2-cyclopentenyl)acetate (3) can be obtained by multi-step conversion of the alkoxycarbonylmethyl group (i.e., -CH2C(=O)OR) of the (1,5,5-trimethyl-2-cyclopentenyl)acetate compound (2) obtained in B to a 2-acetoxyethyl group (i.e., -CH2CH2OAc), as shown in the following reaction formula (see Examples 2-1 to 2-5 below).

[0112]

[0113] The starting material (1,5,5-trimethyl-2-cyclopentenyl) acetate compound (2) is as described above. R in formula (2) is as defined in formula (1), but for reactivity, a straight-chain alkyl group having 1 to 4 carbon atoms is preferred. For reactivity and / or availability, a straight-chain alkyl group having 1 to 3 carbon atoms, i.e., a methyl group, an ethyl group, and a n-propyl group, is more preferred.

[0114] Next, the target substance ethyl 2-(1,5,5-trimethyl-2-cyclopentenyl)acetate (3) will be described below.

[0115] In general formula (3), Ac represents the acetyl group.

[0116] Ethyl 2-(1,5,5-trimethyl-2-cyclopentenyl)ethyl acetate (3) includes (R)-2-(1,5,5-trimethyl-2-cyclopentenyl)ethyl acetate, (S)-2-(1,5,5-trimethyl-2-cyclopentenyl)ethyl acetate, and their racemic mixtures and mixtures of the two enantiomers.

[0117] The method for obtaining 2-(1,5,5-trimethyl-2-cyclopentenyl)ethyl acetate (3) by converting the alkoxycarbonyl methyl group (i.e., -CH2C(=O)OR) of (1,5,5-trimethyl-2-cyclopentenyl)acetate compound (2) in multiple steps to the 2-acetoxyethyl group (i.e., -CH2CH2OAc) can be achieved by combining at least two known methods for converting functional groups.

[0118] As shown in the following reaction formula, an example of a multi-step conversion includes the step of reducing (1,5,5-trimethyl-2-cyclopentenyl)acetate compound (2) with a reducing agent to obtain 2-(1,5,5-trimethyl-2-cyclopentenyl)ethanol (5), and subsequently acetylating the 2-(1,5,5-trimethyl-2-cyclopentenyl)ethanol (5) thus obtained to obtain 2-(1,5,5-trimethyl-2-cyclopentenyl)ethyl acetate (3) (hereinafter referred to as preparation process 1) (see Examples 2-1 and 2-5 below).

[0119]

[0120] As shown in the following reaction formula, another example of a multi-step transformation includes the steps of hydrolyzing (1,5,5-trimethyl-2-cyclopentenyl)acetic acid compound (2) to obtain (1,5,5-trimethyl-2-cyclopentenylacetic acid (6), reducing the (1,5,5-trimethyl-2-cyclopentenylacetic acid (6)) with a reducing agent (as shown in Preparation 1) to obtain 2-(1,5,5-trimethyl-2-cyclopentenyl)ethanol (5), and subsequently acetylifying the 2-(1,5,5-trimethyl-2-cyclopentenyl)ethanol (5) thus obtained to obtain 2-(1,5,5-trimethyl-2-cyclopentenyl)ethyl acetate (3) (hereinafter referred to as Preparation 2) (see Examples 2-2, 2-3, 2-4 and 2-5 below).

[0121]

[0122] (a) The preparation process 1 will be described below.

[0123] The reduction reaction of (1,5,5-trimethyl-2-cyclopentenyl)acetic acid compound (2) can be carried out using a reducing agent, and can be carried out by heating or cooling if necessary.

[0124] The reducing agent used in a reduction reaction can be a known reducing agent and is not subject to specific restrictions.

[0125] Examples of reducing agents include hydrogen; boron compounds such as boranes, alkylboranes, dialkylboranes, and bis(1,2-dimethylpropyl)boranes; metal hydrides such as dialkylsilanes, trialkylsilanes, aluminum hydride, alkylaluminum hydride, dialkylaluminum hydride, sodium hydride, lithium hydride, potassium hydride, and calcium hydride; and metal hydride complexes such as sodium borohydride, lithium borohydride, potassium borohydride, trimethoxysodium borohydride, triethyllithium borohydride, sodium aluminum hydride, lithium aluminum hydride, trimethoxylithium aluminum hydride, diethoxylithium aluminum hydride, tritert-butoxylithium aluminum hydride, and sodium bis(2-methoxyethoxy)aluminum hydride. Metal hydride complexes are preferred considering reactivity and / or yield.

[0126] The amount of reducing agent in the reduction reaction can be arbitrarily set according to the reactivity and / or structure and / or reaction mechanism of the reducing agent. For example, considering reactivity and / or economy, the amount is preferably 0.2 mol to 10.0 mol, more preferably 0.25 mol to 5.0 mol, relative to each mol of (1,5,5-trimethyl-2-cyclopentenyl)acetic acid compound (2).

[0127] The solvent used in a reduction reaction can be any solvent that does not adversely affect the reduction reaction. Examples of solvents used in reduction reactions include water; hydrocarbon solvents such as hexane, heptane, octane, benzene, toluene, and xylene; ether solvents such as diethyl ether, di-n-butyl ether, di-tert-butyl ether, cyclopentyl methyl ether, diethylene glycol diethyl ether, diethylene glycol dimethyl ether, tetrahydrofuran, and 1,4-dioxane; halogen-based solvents such as dichloromethane and chloroform; alcohol solvents such as methanol, ethanol, 1-propanol, and 2-propanol; nitrile solvents such as acetonitrile; and aprotic polar solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, and hexamethylphosphoric triamine. Hydrocarbon and ether solvents are preferred considering reactivity.

[0128] If necessary, the solvent may be used alone or in combination, and may optionally be determined while taking into account the type and / or reactivity of the (1,5,5-trimethyl-2-cyclopentenyl)acetic acid compound (2).

[0129] While taking into account the reactivity and / or solubility of the (1,5,5-trimethyl-2-cyclopentenyl)acetic acid compound (2), the amount of solvent may optionally be determined, for example, taking into account reactivity and / or economy, the amount of solvent is preferably 30 g to 10,000 g, more preferably 50 g to 3,000 g, relative to each mol of the (1,5,5-trimethyl-2-cyclopentenyl)acetic acid compound (2).

[0130] The reduction reaction can be carried out at a temperature that has no adverse effect on the reduction reaction. It is preferably -50°C to 200°C, more preferably -25°C to 100°C, taking into account the yield and / or the formation of byproducts.

[0131] Preferably, the reaction time of the reduction reaction is optimized based on the reactivity of the (1,5,5-trimethyl-2-cyclopentenyl)acetate compound (2) by monitoring the reaction progress using, for example, gas chromatography and / or thin-layer chromatography to confirm the disappearance of the (1,5,5-trimethyl-2-cyclopentenyl)acetate compound (2). For example, taking into account the yield and / or the formation of impurities, the reaction time is preferably from 1 hour to 168 hours, more preferably from 1 hour to 24 hours, and even more preferably from 1 hour to 6 hours.

[0132] The 2-(1,5,5-trimethyl-2-cyclopentenyl)ethanol (5) formed in the reduction reaction can be appropriately separated and / or purified by any purification method commonly used in organic synthesis, such as vacuum distillation and / or various chromatographic methods. Vacuum distillation is preferred for industrial economics. When the target substance 2-(1,5,5-trimethyl-2-cyclopentenyl)ethanol (5) has sufficient purity, the crude product containing 2-(1,5,5-trimethyl-2-cyclopentenyl)ethanol (5) can be used directly in subsequent steps without purification.

[0133] The 2-(1,5,5-trimethyl-2-cyclopentenyl)ethanol (5) to be obtained by reduction reaction includes (R)-2-(1,5,5-trimethyl-2-cyclopentenyl)ethanol, (S)-2-(1,5,5-trimethyl-2-cyclopentenyl)ethanol, and their racemic mixtures and mixtures of the two enantiomers.

[0134] The acetylation method for 2-(1,5,5-trimethyl-2-cyclopentenyl)ethanol (5) obtained by reduction reaction can be any known acetylation method and is not specifically limited. Specific examples of acetylation methods include (i) acetylation reaction between an alcohol compound and an acetyling agent, (ii) dehydration reaction between an alcohol compound and acetic acid, (iii) transesterification reaction between an alcohol compound and an acetate compound, and (iv) conversion of an alcohol compound to an alkylating agent, followed by acetylation with acetic acid or a metal acetate. The target compound of the present invention, ethyl 2-(1,5,5-trimethyl-2-cyclopentenyl)ethanol (3), can be prepared from 2-(1,5,5-trimethyl-2-cyclopentenyl)ethanol (5) as an alcohol compound.

[0135] (i) Acetylation reaction between alcohol compounds and acetylation agents

[0136] The acetylation reaction between alcohol compounds and acetylation agents is usually carried out in the presence of a base or catalyst, and can be carried out by heating or cooling if necessary.

[0137] Examples of acetylation agents include acetyl chloride, acetyl bromide, or acetic anhydride.

[0138] Considering economic efficiency, the amount of acetylation agent is preferably 1.0 mol to 30.0 mol, more preferably 1.0 mol to 5.0 mol, relative to each mol of alcohol compound.

[0139] For example, when acetyl chloride, acetyl bromide, or acetic anhydride is used as an acetylation agent, acetylation can be carried out in the presence of a base.

[0140] Examples of bases in acetylation reactions include amines such as triethylamine, pyridine, N,N-dimethylaminopyridine, and N,N-dimethylaniline; organometallic compounds such as n-butyllithium, methyllithium, and phenyllithium; metal hydroxides such as sodium hydroxide and potassium hydroxide; and metal carbonates such as potassium carbonate, sodium carbonate, and sodium bicarbonate.

[0141] If necessary, the base may be used alone or in combination with it, and may optionally be determined while taking into account the type and / or reactivity of the alcohol compound and / or acetylation agent.

[0142] For economic reasons, the amount of base is preferably 1.0 mol to 50.0 mol, more preferably 1.0 mol to 10.0 mol, relative to each mol of alcohol compound.

[0143] For example, when acetic anhydride is used as an acetylation agent, acetylation can be carried out in the presence of a catalyst.

[0144] Examples of catalysts include inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, and nitric acid; sulfonic acids such as methanesulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid; Lewis acids such as aluminum trichloride, aluminum isopropoxide, zinc chloride, boron trifluoride, boron trichloride, tin tetrachloride, dibutyltin dichloride, titanium tetrachloride, and titanium isopropoxide (IV); and metal acetates such as sodium acetate and potassium acetate.

[0145] If necessary, the catalyst may be used alone or in combination, and may optionally be determined while taking into account the type and / or reactivity of the alcohol compound and / or acetylation agent.

[0146] Considering economic efficiency, the amount of catalyst is preferably 0.001 mol to 1.0 mol, more preferably 0.005 mol to 0.2 mol, relative to each mol of alcohol compound.

[0147] Optionally, the solvent can be used in the acetylation reaction.

[0148] Solvents can be any solvent that does not adversely affect alcohol compounds, acetylation agents, bases, and / or catalysts. Examples of solvents include halogen-based solvents such as dichloromethane and chloroform; hydrocarbon solvents such as hexane, heptane, benzene, and toluene; ether solvents such as diethyl ether, tetrahydrofuran, 1,4-dioxane, and diethylene glycol dimethyl ether; nitrile solvents such as acetonitrile; ketone solvents such as acetone, methyl ethyl ketone, and diisobutyl ketone; ester solvents such as ethyl acetate and butyl acetate; and aprotic polar solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, and hexamethylphosphoric triamine.

[0149] If necessary, the solvent may be used alone or in combination, and may be optionally determined while taking into account the type and / or reactivity of the alcohol compound, acetylation agent, base and / or catalyst.

[0150] For economic reasons, the amount of solvent is preferably greater than 0 g to 10,000 g, more preferably greater than 0 g to 5,000 g, relative to each mol of alcohol compound.

[0151] Note that, depending on the type of alcohol compound, acetylation agent, base, and / or catalyst, acetylation reactions can be carried out without solvents.

[0152] Considering reactivity and / or yield, the reaction temperature for the acetylation reaction is preferably -78°C to 120°C, more preferably -30°C to 80°C.

[0153] Preferably, the reaction time of the acetylation reaction is optimized based on the reactivity of the alcohol compound, acetylation agent, base and / or catalyst by using, for example, gas chromatography and / or thin-layer chromatography to monitor the reaction progress to confirm the disappearance of the alcohol compound. For example, taking into account the yield and / or the formation of impurities, the reaction time is preferably 1 hour to 168 hours, more preferably 1 hour to 24 hours, and even more preferably 1 hour to 18 hours.

[0154] (ii) Dehydration reaction between alcohols and acetic acid

[0155] The dehydration reaction between alcohols and acetic acid is usually carried out in the presence of a catalyst, and can be carried out by heating or cooling if necessary.

[0156] Examples of catalysts used in dehydration reactions include acids or Lewis acids.

[0157] Examples of acids that can act as catalysts include inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, and nitric acid; and organic acids such as trichloroacetic acid, trifluoroacetic acid, methanesulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid. Examples of Lewis acids that can act as catalysts include aluminum trichloride, aluminum dichloroethoxide, aluminum ethoxide, aluminum isopropoxide, zinc diisopropoxide, zinc diethoxide, zinc dimethylethanol, zinc chloride, boron trifluoride, boron trichloride, tin tetrachloride, dibutyltin dichloride, dibutyltin dimethylethanol, dibutyltin oxide, titanium tetrachloride, titanium tetrabromide, titanium methoxide (IV), titanium ethoxide (IV), and titanium isopropoxide (IV).

[0158] If necessary, the catalyst may be used alone or in combination, and may be optionally determined while taking into account the reactivity of the alcohol compound.

[0159] Considering economy and reactivity, the amount of catalyst in the dehydration reaction is preferably 0.001 mol to 1.0 mol, more preferably 0.05 mol to 0.1 mol, relative to each mol of alcohol compound.

[0160] The dehydration reaction can be carried out simultaneously with the removal of water, a byproduct of the reaction. The dehydration reaction can be carried out under normal or reduced pressure conditions by azeotropic distillation to remove water and the reaction solvent, or by using a dehydrating agent added to the reaction system, such as anhydrous magnesium sulfate, molecular sieves, or dicyclohexylcarbodiimide.

[0161] The solvent used in a dehydration reaction can be any solvent that does not adversely affect the alcohol compound and / or catalyst used. Examples of solvents used in dehydration reactions include halogen-based solvents such as dichloromethane and chloroform; hydrocarbon solvents such as hexane, heptane, benzene, and toluene; ether solvents such as diethyl ether, tetrahydrofuran, 1,4-dioxane, and diethylene glycol dimethyl ether; nitrile solvents such as acetonitrile; ketone solvents such as acetone, methyl ethyl ketone, and diisobutyl ketone; and ester solvents such as ethyl acetate and butyl acetate.

[0162] If necessary, the solvent may be used alone or in combination, and may optionally be determined while taking into account the type and / or reactivity of the alcohol compound and / or catalyst.

[0163] For economic reasons, the amount of solvent in the dehydration reaction is preferably greater than 0 g to 10,000 g, more preferably greater than 0 g to 3,000 g, relative to each mol of alcohol compound.

[0164] Note that, depending on the type of alcohol compound and / or catalyst, the dehydration reaction can be carried out without solvent.

[0165] The reaction temperature for the dehydration reaction can be appropriately determined according to the type of alcohol compound and / or catalyst to be used, preferably from -30°C to 200°C, more preferably from 25°C to 100°C, taking into account reactivity and / or yield. When water generated as a byproduct by the dehydration reaction is azeotropically removed together with the solvent, the dehydration reaction is preferably carried out at a reaction temperature not lower than the azeotropic point of the solvent and water under atmospheric or reduced pressure conditions.

[0166] Preferably, the reaction time of the dehydration reaction is optimized according to the type and / or reactivity of the alcohol compound and / or catalyst by using, for example, gas chromatography and / or thin-layer chromatography to monitor the reaction progress to confirm the disappearance of the alcohol compound. For example, taking into account the yield and / or the formation of impurities, the reaction time is preferably 1 hour to 168 hours, more preferably 1 hour to 24 hours, and even more preferably 1 hour to 12 hours.

[0167] (iii) Transesterification reaction between alcohols and acetates

[0168] Transesterification reactions between alcohols and acetates are typically carried out in the presence of a catalyst. The alcohol formed from the acetate in the transesterification reaction can be removed under normal or reduced pressure to promote the reaction, and if necessary, by heating or cooling.

[0169] Examples of acetate compounds used in transesterification reactions include methyl acetate, ethyl acetate, propyl acetate, butyl acetate, and phenyl acetate. Among these acetates, methyl acetate and ethyl acetate are preferred considering economic efficiency, reactivity, and ease of removing alcohols generated as byproducts from the acetate.

[0170] The amount of acetate in the transesterification reaction is preferably 1.0 mol to 30.0 mol, more preferably 1.0 mol to 5.0 mol, relative to each mol of alcohol compound.

[0171] Examples of catalysts in transesterification reactions include acids such as hydrochloric acid, sulfuric acid, trifluoroacetic acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, and Amberlyst 15; alkali metal salts of alcohols such as sodium methoxide, sodium ethoxide, and potassium tert-butoxide; carboxylic acid metal salts such as sodium acetate, potassium acetate, calcium acetate, tin acetate, zinc acetate, and aluminum acetate; and Lewis acids such as aluminum trichloride, aluminum ethoxide, aluminum isopropoxide, zinc diisopropoxide, zinc diethanoloxide, zinc dimethoxide, zinc chloride, boron trifluoride, boron trichloride, tin tetrachloride, dibutyltin dichloride, dibutyltin dimethoxide, dibutyltin oxide, titanium tetrachloride, titanium tetrabromide, titanium methoxide (IV), titanium ethoxide (IV), and titanium isopropoxide (IV).

[0172] Considering yield and / or economy, the amount of catalyst in the transesterification reaction is preferably 0.001 mol to 1.0 mol, more preferably 0.005 mol to 0.1 mol, relative to each mol of alcohol compound.

[0173] The solvent used in transesterification reactions can be appropriately determined from solvents that do not adversely affect the catalyst. Examples of solvents used in transesterification reactions include halogen-based solvents such as dichloromethane and chloroform; hydrocarbon solvents such as hexane, heptane, benzene, and toluene; ether solvents such as diethyl ether, tetrahydrofuran, 1,4-dioxane, and diethylene glycol dimethyl ether; nitrile solvents such as acetonitrile; ketone solvents such as acetone, methyl ethyl ketone, and diisobutyl ketone; and ester solvents such as ethyl acetate and butyl acetate.

[0174] If necessary, the solvent may be used alone or in combination, and optionally determined while taking into account the type and / or reactivity of the alcohol compound, acetate and / or catalyst.

[0175] For economic reasons, the amount of solvent is preferably greater than 0 g to 2,000 g, and most preferably greater than 0 g to 500 g, relative to each mol of alcohol compound.

[0176] Note that, depending on the type of alcohol, acetate, and / or catalyst, transesterification can be carried out in the absence of solvents.

[0177] The reaction temperature for transesterification can be appropriately determined based on the type of alcohol, acetate, and / or catalyst. Generally, the reaction temperature is preferably from 0°C to 200°C, more preferably from 50°C to 150°C. When removing alcohols that are byproducts during transesterification to promote the reaction, the transesterification reaction is preferably carried out at a reaction temperature not lower than the boiling point of the alcohol to be removed under atmospheric or reduced pressure.

[0178] Preferably, the reaction time of the transesterification reaction is optimized based on the reactivity of the alcohol compound and / or acetate by monitoring the reaction progress using, for example, gas chromatography and / or thin-layer chromatography to confirm the disappearance of the alcohol compound and / or acetate. For example, taking into account the yield and / or the formation of impurities, the reaction time is preferably 1 hour to 168 hours, more preferably 1 hour to 24 hours, and even more preferably 1 hour to 12 hours.

[0179] (iv) Convert the alcohol compound into an alkylating agent, followed by acetoxylation with acetic acid or a metal acetate.

[0180] If necessary, the alcohol compound can be converted into an alkylating agent, followed by acetoxylation with acetic acid or a metal acetate, which can be carried out by heating or cooling. Examples of metal acetates include sodium acetate and potassium acetate.

[0181] Typically, alcohols can be converted into alkylating agents corresponding to the alcohols, such as halides like chlorides, bromides, and iodides; sulfonates, such as methanesulfonates, benzenesulfonates, and p-toluenesulfonates, which can then be acetoxylated. When acetoxylation is performed using acetic acid, it is carried out in the presence of a base, while when acetoxylation is performed using metal acetates, it can be carried out in the absence of a base.

[0182] Examples of bases in acetoxylation reactions include amines such as triethylamine, pyridine, N,N-dimethylaminopyridine, and dimethylaniline; organometallic compounds such as n-butyllithium, methyllithium, and phenyllithium; metal hydroxides such as sodium hydroxide and potassium hydroxide; metal carbonates such as potassium carbonate, sodium carbonate, and sodium bicarbonate; and metal hydrides such as sodium hydride and potassium hydride.

[0183] If necessary, the base may be used alone or in combination with it, and may optionally be determined while taking into account the type and / or reactivity of the alkylating agent.

[0184] Considering economic efficiency, the amount of base is preferably from 1.0 mol to 50.0 mol per mol of alkylating agent, and more preferably from 1.0 mol to 10.0 mol per mol of alkylating agent.

[0185] The solvent used in the acetoxylation reaction can be suitably determined from any solvent that has no adverse effect on the acetoxylation reaction. Examples of solvents used in the acetoxylation reaction include halogen-based solvents such as dichloromethane and chloroform; hydrocarbon solvents such as hexane, heptane, benzene, and toluene; ether solvents such as diethyl ether, tetrahydrofuran, 1,4-dioxane, and ethylene glycol dimethyl ether; nitrile solvents such as acetonitrile; ketone solvents such as acetone, methyl ethyl ketone, and diisobutyl ketone; ester solvents such as ethyl acetate and butyl acetate; and aprotic polar solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, and hexamethylphosphoric triamine.

[0186] If necessary, the solvent may be used alone or in combination, and may optionally be determined while taking into account the type and / or reactivity of the alkylating agent and / or acetic acid or metal acetate.

[0187] For economic reasons, the amount of solvent in the acetoxylation reaction is preferably greater than 0 g to 5,000 g, more preferably greater than 0 g to 1,000 g, relative to each mol of alkylating agent.

[0188] Considering reactivity and / or yield, the reaction temperature for acetoxylation is preferably from -30°C to 250°C, more preferably from 25°C to 180°C.

[0189] Preferably, the reaction time of the acetoxylation reaction is optimized based on the reactivity of the alkylating agent and / or acetic acid or metal acetate by monitoring the reaction progress using, for example, gas chromatography and / or thin-layer chromatography to confirm the disappearance of the alkylating agent. For example, this time is preferably 1 hour to 168 hours, more preferably 1 hour to 24 hours, and even more preferably 1 hour to 12 hours, taking into account yield and / or the formation of impurities.

[0190] As described in (i) to (iv) above, ethyl 2-(1,5,5-trimethyl-2-cyclopentenyl)ethanol (5) formed by acetylation can be appropriately separated and / or purified by any purification method commonly used in organic synthesis, such as vacuum distillation and / or various chromatographic methods. Vacuum distillation is preferred for industrial economics. When the target substance ethyl 2-(1,5,5-trimethyl-2-cyclopentenyl)ethanol (3) has sufficient purity, the crude product containing ethyl 2-(1,5,5-trimethyl-2-cyclopentenyl)ethanol (3) can be used directly without purification.

[0191] (b) Next, the preparation process 2 will be described below.

[0192] The hydrolysis of (1,5,5-trimethyl-2-cyclopentenyl)acetic acid ester (2) to 2-(1,5,5-trimethyl-2-cyclopentenyl)ethyl acetate (3) can be carried out using known methods, and may be carried out by heating or cooling if necessary.

[0193] For example, hydrolysis can be carried out under alkaline conditions in the presence of a base, under acidic conditions in the presence of an acid, or under neutral conditions in the presence of a salt or a silane halide.

[0194] Examples of bases used for hydrolysis under alkaline conditions include hydroxide salts such as sodium hydroxide, lithium hydroxide, potassium hydroxide, and barium hydroxide; carbonates or bicarbonates such as sodium carbonate, potassium carbonate, sodium bicarbonate, and potassium bicarbonate; and metal alkoxides such as sodium methoxide, sodium ethoxide, sodium tert-butoxide, lithium methoxide, lithium ethoxide, lithium tert-butoxide, potassium methoxide, potassium ethoxide, and potassium tert-butoxide.

[0195] If necessary, the base may be used alone or in combination with it, and may optionally be determined while taking into account the type and / or reactivity and / or selectivity of the (1,5,5-trimethyl-2-cyclopentenyl)acetic acid compound (2).

[0196] Examples of acids used for hydrolysis under acidic conditions include inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, and nitric acid; organic acids such as acetic acid, formic acid, oxalic acid, trifluoroacetic acid, methanesulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid; and Lewis acids such as aluminum trichloride, aluminum ethoxide, aluminum isopropoxide, boron trifluoride, boron trichloride, boron tribromide, tin tetrachloride, tin tetrabromide, dibutyltin dichloride, dibutyltin dimethoxide, dibutyltin oxide, titanium tetrachloride, titanium tetrabromide, titanium methoxide (IV), titanium ethoxide (IV), and titanium isopropoxide (IV).

[0197] If necessary, the acid may be used alone or in combination with it, and may optionally be determined while taking into account the type and / or reactivity and / or selectivity of the (1,5,5-trimethyl-2-cyclopentenyl)acetic acid compound (2).

[0198] Examples of salts and silane halides used for hydrolysis under neutral conditions include salts such as lithium iodide, lithium bromide, sodium cyanide, potassium cyanide, lithium methanethiol, and sodium benzenethiolate; and silane halides such as trimethyliodosilane and trimethylbromosilane.

[0199] If necessary, the salt or halosilane may be used alone or in combination, and may optionally be determined while taking into account the type and / or reactivity and / or selectivity of the (1,5,5-trimethyl-2-cyclopentenyl)acetic acid compound (2).

[0200] Considering yield and / or the formation of impurities, the hydrolysis reaction is preferably carried out under alkaline conditions, more preferably in the presence of hydroxide salts, carbonates or bicarbonates.

[0201] Depending on the reactivity of the (1,5,5-trimethyl-2-cyclopentenyl)acetate compound (2), the amount of base, acid, salt or halosilane used in the hydrolysis reaction can be arbitrarily set from a very low catalytic amount to a large excess. For example, taking into account the reaction time and / or the formation of impurities as byproducts, the amount is preferably 0.1 mol to 50.0 mol, more preferably 0.5 mol to 10.0 mol, relative to each mol of (1,5,5-trimethyl-2-cyclopentenyl)acetate compound (2).

[0202] The solvent used in the hydrolysis reaction can be any solvent that does not adversely affect the hydrolysis reaction. Examples of solvents used in the hydrolysis reaction include water; alcohol solvents, such as methanol, ethanol, isopropanol, and tert-butanol; ether solvents, such as diethyl ether, di-n-butyl ether, di-tert-butyl ether, tetrahydrofuran, 1,4-dioxane, and diethylene glycol dimethyl ether; hydrocarbon solvents, such as hexane, heptane, benzene, toluene, and xylene; aprotic polar solvents, such as N,N-dimethylformamide, N,N-dimethylacetamide, 1,3-dimethyl-2-imidazolinone, dimethyl sulfoxide, and hexamethylphosphoric triamine; and nitrile solvents, such as acetonitrile. Considering reactivity, alcohol solvents and ether solvents are preferred.

[0203] If necessary, the solvent may be used alone or in combination, and may optionally be determined while taking into account the type and / or reactivity of the (1,5,5-trimethyl-2-cyclopentenyl)acetic acid compound (2).

[0204] The amount of solvent used may be optionally determined while taking into account the reactivity and / or solubility of the (1,5,5-trimethyl-2-cyclopentenyl)acetic acid compound (2), for example, preferably 30 g to 20,000 g, more preferably 500 g to 8,000 g, relative to each mol of the (1,5,5-trimethyl-2-cyclopentenyl)acetic acid compound (2), taking into account reactivity and / or economy.

[0205] The reaction temperature for the hydrolysis reaction can be optionally determined while taking into account the reactivity of the (1,5,5-trimethyl-2-cyclopentenyl)acetic acid compound (2) and / or the formation of impurities. Taking into account reactivity and / or the formation of impurities, the reaction temperature is preferably from -60°C to 250°C, more preferably from 0°C to 100°C.

[0206] Preferably, the reaction time of the hydrolysis reaction is optimized based on the reactivity of the (1,5,5-trimethyl-2-cyclopentenyl)acetate compound (2) by monitoring the reaction progress using, for example, gas chromatography and / or thin-layer chromatography to confirm the disappearance of the (1,5,5-trimethyl-2-cyclopentenyl)acetate compound (2) as the substrate. For example, considering the yield and / or the formation of impurities, the reaction time of the hydrolysis reaction is preferably 1 hour to 168 hours, more preferably 1 hour to 24 hours, and even more preferably 1 hour to 12 hours.

[0207] (1,5,5-trimethyl-2-cyclopentenyl)acetic acid (6) obtained by hydrolysis reaction can be processed as follows: it is dissolved under alkaline conditions to form a carboxylate in the aqueous layer, the aqueous layer containing the carboxylate is extracted, the organic layer is separated, the obtained aqueous layer is acidified, and the aqueous layer is re-extracted with an organic solvent.

[0208] The (1,5,5-trimethyl-2-cyclopentenyl)acetic acid (6) formed during the hydrolysis reaction can be appropriately separated and / or purified using any purification method commonly used in organic synthesis, such as vacuum distillation and / or various chromatographic methods. Vacuum distillation is preferred for industrial economics. When the target compound (1,5,5-trimethyl-2-cyclopentenyl)acetic acid (6) has sufficient purity, the crude product containing (1,5,5-trimethyl-2-cyclopentenyl)acetic acid (6) can be used directly in subsequent steps without purification.

[0209] (1,5,5-trimethyl-2-cyclopentenyl)acetic acid (6) includes (R)-(1,5,5-trimethyl-2-cyclopentenyl)acetic acid, (S)-(1,5,5-trimethyl-2-cyclopentenyl)acetic acid, and their racemic mixtures and mixtures of the two enantiomers.

[0210] The method of reducing (1,5,5-trimethyl-2-cyclopentenyl)acetic acid (6) with a reducing agent to obtain 2-(1,5,5-trimethyl-2-cyclopentenyl)ethanol (5) can be carried out in a similar manner to the reduction of (1,5,5-trimethyl-2-cyclopentenyl)acetic acid ester compound (2) to 2-(1,5,5-trimethyl-2-cyclopentenyl)ethanol (5) in the aforementioned preparation process 1.

[0211] The method for acetylation of 2-(1,5,5-trimethyl-2-cyclopentenyl)ethanol (5) obtained by reduction reaction to obtain ethyl 2-(1,5,5-trimethyl-2-cyclopentenyl)acetate (3) is as described in the acetylation reaction in preparation process 1 above.

[0212] As described above, (1,5,5-trimethyl-2-cyclopentenyl)acetal compound (1) was dehydrohalogenated in the presence of a base and then rearranged to obtain (1,5,5-trimethyl-2-cyclopentenyl)acetate compound (2) within an industrially readily applicable reaction temperature range without the use of flammable and industrially expensive starting materials. Then, the alkoxycarbonyl methyl group (i.e., -CH2C(=O)OR) of (1,5,5-trimethyl-2-cyclopentenyl)acetate compound (2) was subjected to a multi-step transformation to convert to a 2-acetoxyethyl group (i.e., -CH2CH2OAc), thereby efficiently and industrially preparing 2-(1,5,5-trimethyl-2-cyclopentenyl)acetate (3).

[0213] Example

[0214] The present invention will be described with reference to the following embodiments and comparative examples. It should be understood that the present invention is not limited to or not construed as being limited by these embodiments.

[0215] Unless otherwise specified, the term "purity" as used herein refers to the percentage of area determined by gas chromatography (hereinafter also referred to as "GC").

[0216] The term "yield" is calculated as a percentage of the area determined by GC.

[0217] The yield was calculated using the following equation, taking into account the purity (%GC) of the starting materials and the product.

[0218] Yield (%) = {[(mass of product obtained in the reaction × % GC) / molecular weight of product] ÷ [(mass of starting material × % GC) / molecular weight of starting material]} × 100

[0219] GC conditions are as follows:

[0220] GC conditions used to determine “purity” and “product ratio”: GC: GC-2010 capillary gas chromatograph (Shimadzu Corporation); column: DB-5, 0.25μm×0.25mmφ×30m; carrier gas: He (1.55mL / min); detector: FID; column temperature: 60℃, hold for 3 minutes, increase at 10℃ / min, up to 230℃.

[0221] As used in this article, Et represents the ethyl group. i Pr represents the isopropyl group, and n Bu represents the n-butyl group.

[0222] Synthesis example

[0223] The following synthetic examples 1-1 to 1-4 describe a method for preparing alkyl 3,4,4-trimethyl-2-cyclopentenyl acetals (1) as shown in the following reaction formula (1).

[0224]

[0225] Synthesis example 1-1

[0226] Preparation of bromoacetaldehyde ethyl 3,4,4-trimethyl-2-cyclopentenyl acetal (1: R = Et; Y = Br)

[0227]

[0228] The air in the reactor, equipped with a stirrer, condenser, and thermometer, was purged with nitrogen. Then, bromine (Br2) (26.36 g: 0.165 mol) and dichloromethane (CH2Cl2) (750.0 g) were added to the reactor, and the liquid temperature was lowered to -5°C to 0°C. Ethyl vinyl ether (7:R=Et) (12.98 g: 0.180 mol) was added dropwise over 90 minutes while maintaining the liquid temperature at -5°C to 0°C. After the addition was complete, the reaction mixture was stirred for 30 minutes at the liquid temperature at -5°C to 0°C. After stirring, diisopropylethylamine was added over 10 minutes at the liquid temperature at -5°C to 0°C. i Pr)2NEt)(23.27g: 0.180mol). After the addition was complete, 3,4,4-trimethyl-2-cyclopenten-1-ol (8) (18.93g: 0.150mol, purity 94.9%) was added dropwise over 1 hour at a liquid temperature of -10°C to -5°C. After the addition was complete, the reaction mixture was stirred at a liquid temperature of -5°C to 0°C for 1 hour, and then stirred at a liquid temperature of 20°C to 25°C for 3 hours.

[0229] After stirring, a 3.5 wt% aqueous solution of sodium bicarbonate (500.0 g) was added to the reaction mixture to quench the reaction. After quenching, the reaction mixture was separated into an organic layer and an aqueous layer. The resulting organic layer was washed successively with water (300.0 g) and a 10.0 wt% aqueous solution of sodium chloride (300.0 g). The solvent was removed from the washed organic layer under reduced pressure, and the crude product was then purified by vacuum distillation to obtain bromoacetaldehyde ethyl 3,4,4-trimethyl-2-cyclopentenyl acetal (1:R=Et;Y=Br) (36.84 g: 0.133 mol, yield 88.6%, purity 91.8%).

[0230] The following are various spectral data for bromoacetaldehyde ethyl 3,4,4-trimethyl-2-cyclopentenyl acetal (1:R=Et;Y=Br) prepared in this manner.

[0231] Nuclear magnetic resonance spectroscopy: 1H-NMR (500MHz, CDCl3): δ1.00(1.5H,s),1.00(1.5H,s),1.10(1.5H,s),1.11(1.5H,s),1.22(1.5H,t,J=6.9 Hz), 1.23 (1.5H, t, J = 7.1Hz), 1.66 (1.5H, t, J = 1.6Hz), 1.66 (1.5H, t, J = 1.5Hz), 1.75 (0.5H, q, J = 4.4Hz), 1. 77(0.5H,q,4.4Hz),2.02(0.5H,q,J=5.7Hz),2.05(0.5H,q,J=5.7Hz),3.32-3.37(m,2H),3.53-3.62(1H,m) ,3.63-3.73(1H,m),4.62-4.68(1H,m),4.71(0.5H,t,J=2.9Hz),4.73(0.5H,t,J=3.1Hz),5.35(1H,br)ppm. 13 C-NMR (126MHz, CDCl3): δ12.29,15.13,15.22,27.31,27.35,27.73,27.82,32.29,32.42,45.09,45. 16,47.12,47.99,61.34,61.89,79.95,80.02,100.53,101.00,123.24,123.58,153.88,153.93ppm.

[0232] Mass spectrometry EI (70eV): m / z 152,151,125,123,93,91,83,81,79,77,72,57,43,29.

[0233] Infrared absorption spectrum (D-ATR): ν (cm) -1 )583,683,829,892,1032,1055,1115,1190,1223,1338,1361,1376,1437,1465,1653,2866,2929,2956,3046.

[0234] Synthesis example 1-2

[0235] Preparation of bromoacetaldehyde ethyl 3,4,4-trimethyl-2-cyclopentenyl acetal (1: R = Et; Y = Br)

[0236]

[0237] The procedure for the synthesis of Example 1-1 was repeated, except that triethylamine (NEt3) (18.21 g: 0.180 mol) was used instead of diisopropylethylamine.i Using Pr)2NEt) as a base, the resulting product is bromoacetaldehyde ethyl 3,4,4-trimethyl-2-cyclopentenyl acetal (1:R=Et; Y=Br) (30.60 g: 0.110 mol, yield 73.3%, purity 89.2%).

[0238] The various spectral data of the bromoacetaldehyde ethyl 3,4,4-trimethyl-2-cyclopentenyl acetal (1:R=Et;Y=Br) prepared in this way are the same as those determined in Synthesis Example 1-1.

[0239] Synthesis Example 1-3

[0240] Preparation of bromoacetaldehyde isopropyl 3,4,4-trimethyl-2-cyclopentenyl acetal (1:R= i Pr;Y=Br)

[0241]

[0242] The procedure for synthesizing Example 1-1 was repeated, except that isopropyl vinyl ether (7:R= i Pr (15.50 g: 0.180 mol) was used in place of ethyl vinyl ether (7: R = Et), thus yielding bromoacetaldehyde isopropyl 3,4,4-trimethyl-2-cyclopentenyl acetal (1: R = Et). i Pr;Y=Br)(41.19g: 0.141mol, yield 94.3%, purity 87.8%).

[0243] The following is how bromoacetaldehyde isopropyl 3,4,4-trimethyl-2-cyclopentenyl acetal (1:R=) was prepared. i Various spectral data of Pr; Y = Br).

[0244] Nuclear magnetic resonance spectroscopy: 1 H-NMR (500MHz, CDCl3): δ0.97(1.5H,s),0.97(1.5H,s),1.05(1.5H,s),1.05(1.5H,s) ,1.10(3H,d,J=6.0Hz),1.12(3H,dd,J=6.3,3.0Hz),1.62-1.65(4H,m),1.97(0.5H,dd, J=13.2,7.0Hz),2.02(0.5H,dd,J=13.2,7.0Hz),3.35-3.41(2H,m),3.82-3.86(1H,m) ,4.62(1H,m),4.69(0.5H,t,J=5.1Hz),4.71(0.5H,t,J=5.1),5.35(1H,d,22.8Hz)ppm. 13C-NMR (126MHz, CDCl3): δ11.97,12.02,22.14,22.35,23.02,23.06,26.97,27.57,27.58,34.00,34.04,44 .51,44.59,46.96,47.69,68.39,68.51,78.23,78.24,98.62,98.78,123.96,124.25,152.10,152.13ppm.

[0245] Mass spectrometry EI (70eV): m / z 168,167,151,125,110,109,93,91,77,58,43,27.

[0246] Infrared absorption spectrum (D-ATR): ν (cm) -1 )681,829,1026,1124,1171,1202,1337,1380,1421,1437,1466,2867,2929,2969,3045.

[0247] Synthesis Example 1-4

[0248] Preparation of bromoacetaldehyde n-butyl 3,4,4-trimethyl-2-cyclopentenyl acetal (1:R= n Bu;Y=Br)

[0249]

[0250] Repeat the procedure of Example 1-1, except that n-butyl vinyl ether (7:R= n Bu (18.03 g: 0.180 mol) was used to replace ethyl vinyl ether (7:R = Et), thus yielding bromoacetaldehyde n-butyl 3,4,4-trimethyl-2-cyclopentenyl acetal (1:R = n Bu; Y = Br)(34.62 g: 0.113 mol, yield 75.6%, purity 84.0%).

[0251] The following is how bromoacetaldehyde n-butyl 3,4,4-trimethyl-2-cyclopentenyl acetal (1:R=) was prepared. n Various spectral data of Bu; Y = Br).

[0252] Nuclear magnetic resonance spectroscopy: 1H-NMR (500MHz, CDCl3): δ0.88(3H,t,J=7.5Hz),0.97(3H,s),1.05(3H,s),1.34(2 H,sextd,J=7.5,2.4Hz),1.46-1.51(2H,m),1.63-1.66(4H,m),1.98(0.5H,q,J=6. 6Hz),2.01(0.5H,q,J=6.6Hz),3.39-3.47(3H,m),3.50-3.57(1H,m),4.60-4.62(1 H, m), 4.67 (1H, q, J = 5.6Hz), 5.33 (0.5H, t, J = 1.5Hz), 5.37 (0.5H, t, J = 1.5Hz) ppm. 13 C-NMR (126MHz, CDCl3): δ11.97,12.02,13.69,18.78,26.95,27.56,31.29,31.31,33.25,33.29,44.51 ,44.59,46.87,47.55,65.03,65.45,79.11,79.21,99.94,100.23,123.82,124.22,152.20,152.31ppm.

[0253] Mass spectrometry EI (70eV): m / z 181,179,151,125,109,93,91,77,57,41.

[0254] Infrared absorption spectrum (D-ATR): ν (cm) -1 )684,829,1036,1114,1187,1224,1338,1360,1377,1435,1465,1653,2869,2933,2957,3047.

[0255] Example 1

[0256] Examples 1-1 to 1-6 below describe a method for preparing (1,5,5-trimethyl-2-cyclopentenyl) acetate compound (2) from a haloacetal alkyl 3,4,4-trimethyl-2-cyclopentenyl acetal compound (1), as shown in the following reaction formula.

[0257]

[0258] Example 1-1

[0259] Preparation of ethyl (1,5,5-trimethyl-2-cyclopentenyl) acetate (2:R=Et)

[0260]

[0261] The air in the reactor, equipped with a stirrer, condenser, and thermometer, was purged with nitrogen. Then, bromoacetaldehyde ethyl 3,4,4-trimethyl-2-cyclopentenyl acetal (1:R=Et;Y=Br) (27.72 g: 0.100 mol, purity 92.0%) and N,N-dimethylformamide (DMF) (280.0 g) obtained according to Synthesis Example 1-1 were added to the reactor, and the mixture was then cooled to a liquid temperature of 0°C to 5°C. Potassium tert-butoxide (t-BuOK) (12.34 g: 0.110 mol) was added over 30 minutes to the mixture, which was maintained at a liquid temperature of 0°C to 5°C. After the addition was complete, the reaction mixture was maintained at a liquid temperature of 20°C to 25°C for 4 hours.

[0262] After the reaction, the reaction mixture was heated to 100°C and stirred for 5 hours. After stirring, the reaction mixture was cooled to 0°C to 5°C, and water (250.0 g) was added to the reactor to quench the reaction. Diethyl ether (300.0 g) was further added to the reactor to extract the mixture and separate its layers into an organic layer and an aqueous layer. The organic layer was washed with a 10% by weight aqueous solution of sodium chloride (300.0 g). The solvent was removed from the washed organic layer under reduced pressure, and the crude product was then purified by silica gel column chromatography to obtain ethyl(1,5,5-trimethyl-2-cyclopentenyl) acetate (2:R=Et) (9.76 g: 0.050 mol, yield 49.7%, purity 82.2%).

[0263] The following are various spectral data for ethyl (1,5,5-trimethyl-2-cyclopentenyl) acetate (2:R=Et) prepared in this manner.

[0264] Nuclear magnetic resonance spectroscopy: 1 H-NMR (500MHz, CDCl3): δ0.92(3H,s),0.96(3H,s),0.96(3H,s),1.25(3H,t,J=7.3Hz), 2.09(1H,dt,J=15.7,2.1Hz), 2.16(1H,dt,J=16.1, 2.2Hz), 2.18(1H,d,J=13.4Hz), 2.31(1H,d,J=13.4Hz), 4.11(2H,q,J=7.1Hz), 5.62(1H,dt,J=5.7,2.4Hz), 5.77(1H,dt,J=5.7,1.9Hz)ppm. 13 C-NMR (126MHz, CDCl3): δ14.27,19.79,23.95,24.47,40.78,44.04,46.64,49.81,59.97,127.77,138.79,173.07ppm.

[0265] Mass spectrometry EI (70 eV): m / z 196 (M) + ),181,167,150,135,122,109,108,107,93,91,81,79,77,67,55,41,28.

[0266] Infrared absorption spectrum (D-ATR): ν (cm) -1 )716,742,956,1034,1131,1187,1213,1294,1336,1367,1448,1463,1734,2843,2872,2968,2052.

[0267] Examples 1-2

[0268] Preparation of ethyl (1,5,5-trimethyl-2-cyclopentenyl) acetate (2:R=Et)

[0269] Examples 1-2 were carried out in the same manner as Examples 1-1, except that the reaction mixture was heated to 140°C and stirred for 9 hours instead of being heated to 100°C and stirred for 5 hours in Example 1-1. As a result, ethyl (1,5,5-trimethyl-2-cyclopentenyl) acetate (2:R=E) (9.38 g: 0.048 mol, yield 47.8%, purity 80.0%) was obtained.

[0270] The spectral data of the ethyl (1,5,5-trimethyl-2-cyclopentenyl) acetate (2:R=Et) thus prepared are the same as those determined in Examples 1-1.

[0271] Examples 1-3

[0272] Preparation of ethyl (1,5,5-trimethyl-2-cyclopentenyl) acetate (2:R=Et)

[0273]

[0274] The procedure of Example 1-1 was repeated, except that sodium tert-butoxide (t-BuONa) (10.57 g: 0.110 mol) was used instead of potassium tert-butoxide (t-BuOK) used as the base in Example 1-1, and thus ethyl (1,5,5-trimethyl-2-cyclopentenyl) acetate (2:R=Et) (8.62 g: 0.044 mol, yield 43.9%, purity 83.7%) was obtained.

[0275] The spectral data of the ethyl (1,5,5-trimethyl-2-cyclopentenyl) acetate (2:R=Et) thus prepared are the same as those determined in Examples 1-1.

[0276] Examples 1-4

[0277] Preparation of ethyl (1,5,5-trimethyl-2-cyclopentenyl) acetate (2:R=Et)

[0278]

[0279] The procedure of Example 1-1 was repeated, except that diethylene glycol dimethyl ether (Diglyme) (280.0 g) was used instead of N,N-dimethylformamide (DMF) used as a solvent in Example 1-1, and thus ethyl (1,5,5-trimethyl-2-cyclopentenyl) acetate (2:R=Et) (9.50 g: 0.048 mol, yield 48.4%, purity 84.0%) was obtained.

[0280] The spectral data of the ethyl (1,5,5-trimethyl-2-cyclopentenyl) acetate (2:R=Et) thus prepared are the same as those determined in Examples 1-1.

[0281] Examples 1-5

[0282] Preparation of isopropyl (1,5,5-trimethyl-2-cyclopentenyl) acetate (2:R= i Pr)

[0283]

[0284] Repeat the procedure of Examples 1-1, except that bromoacetaldehyde isopropyl 3,4,4-trimethyl-2-cyclopentenyl acetal (1:R=) obtained according to Synthetic Examples 1-3 is used. i Pr; Y = Br)(29.12 g: 0.100 mol, purity 95.0%) was used instead of bromoacetaldehyde ethyl 3,4,4-trimethyl-2-cyclopentenyl acetal (1: R = Et; Y = Br) used as the reaction substrate in Example 1-1, and vacuum distillation was used instead of silica gel column chromatography purification in Example 1-1. Therefore, isopropyl (1,5,5-trimethyl-2-cyclopentenyl) acetate (2: R = i Pr)(6.37g: 0.030mol, yield 30.3%, purity 84.5%).

[0285] The following is how isopropyl (1,5,5-trimethyl-2-cyclopentenyl) acetate (2:R=) prepared. i Various spectral data of Pr).

[0286] Nuclear magnetic resonance spectroscopy: 1H-NMR (500MHz, CDCl3): δ0.93(3H,s),0.97(6H,s),1.24(6H,d,6.0Hz),2.09(1H,dt,J=16.0,1.8Hz),2.15-2.19( 2H,m),2.29(1H,d,13.2Hz),5.01(1H,sep,J=6.6Hz),5.63(1H,dt,J=5.7,2.4Hz),5.79(1H,dt,J=6.0,1.8Hz)ppm. 13 C-NMR (126MHz, CDCl3): δ19.98,22.03,22.05,24.05,24.72,41.22,44.22,46.79,50.03,67.43,127.86,139.00,172.80ppm.

[0287] Mass spectrometry EI (70 eV): m / z 210 (M + ),167,153,135,121,109,108,107,93,91,81,67,55,43,27.

[0288] Infrared absorption spectrum (D-ATR): ν (cm) -1 )716,741,964,1108,1182,1215,1278,1293,1319,1374,1386,1450,1468,1687,1730,2874,2935,2974,3053.

[0289] Examples 1-6

[0290] Preparation of n-butyl(1,5,5-trimethyl-2-cyclopentenyl) acetate (2:R= n Bu)

[0291]

[0292] The procedure of Examples 1-1 was repeated, except that bromoacetaldehyde n-butyl 3,4,4-trimethyl-2-cyclopentenyl acetal (1:R=) obtained in Synthetic Examples 1-4 was used. n Bu; Y = Br)(30.53 g: 0.100 mol, purity 84.0%) was used instead of bromoacetaldehyde ethyl 3,4,4-trimethyl-2-cyclopentenyl acetal (1: R = Et; Y = Br) used as the reaction substrate in Examples 1-1, and the crude product was purified by vacuum distillation instead of silica gel column chromatography used in Examples 1-1, thus obtaining n-butyl (1,5,5-trimethyl-2-cyclopentenyl) acetate (2: R = nBu (4.98g: 0.022mol, yield 22.2%, purity 64.5%).

[0293] The following is how n-butyl (1,5,5-trimethyl-2-cyclopentenyl) acetate (2:R=) was prepared. n Bu) various spectral data.

[0294] Nuclear magnetic resonance spectroscopy: 1 H-NMR (500MHz, CDCl3): δ0.93-0.95(6H,m),0.97(6H,s),1.35-1.42(3H,m),1.61(3H,quin,J=7.4Hz),2.05(1H,d,J=15.6H z), 2.16-2.21 (2H, m), 2.32 (1H, d, J = 13.2Hz), 4.06 (2H, t, J = 6.6Hz), 5.64 (1H, dt, J = 5.7, 2.6Hz), 5.78 (1H, d, J = 6.0Hz) ppm. 13 C-NMR (126MHz, CDCl3): δ13.85,19.37,20.00,24.11,24.65,30.85,41.00,44.21,46.81,49.98,64.17,127.96,138.96,173.41ppm.

[0295] Mass spectrometry EI (70 eV): m / z 224 (M + ),209,167,153,135,122,109,108,107,93,81,67,55,41,29.

[0296] Infrared absorption spectrum (D-ATR): ν (cm) -1 )716,965,1023,1072,1131,1186,1212,1277,1293,1341,1365,1373,1468,1734,2873,2934,2960,3053.

[0297] Example 2

[0298] Examples 2-1 to 2-5 below describe a method for preparing 2-(1,5,5-trimethyl-2-cyclopentenyl)ethyl acetate (3) from (1,5,5-trimethyl-2-cyclopentenyl)acetic acid compound (2), as shown in the following reaction formula.

[0299]

[0300] Example 2-1

[0301] Preparation of 2-(1,5,5-trimethyl-2-cyclopentenyl)ethanol (5) (according to the aforementioned preparation process 1)

[0302]

[0303] The air in the reactor, equipped with a stirrer, condenser, and thermometer, was purged with nitrogen. Then, lithium aluminum hydride (LiALH4) (8.35 g: 0.220 mol) and tetrahydrofuran (THF) (230.0 g) were added to the reactor, and the mixture was stirred at 20°C to 25°C for 2 hours to disperse the lithium aluminum hydride. The temperature of the dispersion was adjusted to 0°C to 5°C, and a solution of ethyl (1,5,5-trimethyl-2-cyclopentenyl) acetate (2:R=Et) (39.26 g: 0.200 mol) in tetrahydrofuran (60.0 g) obtained in Example 1-1 was added dropwise to the reactor at a liquid temperature of 10°C to 15°C for 0.5 hours. After the addition was complete, the reaction mixture was stirred at a liquid temperature of 10°C to 15°C for 1 hour, and then at a liquid temperature of 25°C to 30°C for 2 hours. The reaction mixture was cooled to no more than 5°C, and then water (9.5 g), a 10% by weight aqueous solution of sodium hydroxide (38.0 g), and tetrahydrofuran (30.0 g) were added dropwise to the reactor at a liquid temperature of 0°C to 15°C. After the addition was complete, the reaction mixture was stirred at a liquid temperature of 25°C to 35°C for 1 hour. After stirring, the reaction mixture was filtered, and the solvent was removed from the filtrate under reduced pressure to obtain 2-(1,5,5-trimethyl-2-cyclopentenyl)ethanol (5) (28.14 g: 0.182 mol, yield 91.2%, purity 86.7%). The purity of the 2-(1,5,5-trimethyl-2-cyclopentenyl)ethanol (5) obtained therefrom allows the product (5) to be used without further purification in subsequent processes.

[0304] The following are various spectral data of 2-(1,5,5-trimethyl-2-cyclopentenyl)ethanol (5) prepared in this way.

[0305] Nuclear magnetic resonance spectroscopy: 1 H-NMR (500MHz, CDCl3): δ0.87(3H,s),0.92(3H,s),0.94(3H,s),1.49-1.68(3H,m),2.11(1H,d,J=2.3Hz ), 2.12 (1H, d, J = 1.9Hz), 3.65-3.77 (2H, m), 5.55 (1H, dt, J = 5.8, 1.9Hz), 5.61 (1H, dt, J = 5.8, 2.3Hz) ppm. 13C-NMR (126MHz, CDCl3): δ19.43, 23.91, 24.72, 39.20, 44.00, 46.78, 49.45, 60.68, 128.17, 139.09ppm.

[0306] Mass spectrometry EI (70 eV): m / z 154 (M) + ),139,121,109,95,93,81,79,67,55,41,31.

[0307] Infrared absorption spectrum (D-ATR): ν (cm) -1 )716,740,759,1021,1050,1080,1129,1364,1451,2843,2960,3050,3326.

[0308] Example 2-2

[0309] Preparation of (1,5,5-trimethyl-2-cyclopentenyl)acetic acid (6) (according to the aforementioned preparation process 2)

[0310]

[0311] The air in the reactor, equipped with a stirrer, condenser, and thermometer, was purged with nitrogen. Then, ethyl (1,5,5-trimethyl-2-cyclopentenyl) acetate (2:R=Et) (19.63 g: 0.100 mol, purity 82.2%), methanol (70.0 g), and tetrahydrofuran (THF) (150.0 g) obtained according to Examples 1-1 were added to the reactor, and the mixture was heated to a liquid temperature of 50°C. A 5% by weight aqueous solution of sodium hydroxide (NaOHaq.) (380.0 g: 0.475 mol) was added dropwise to the reactor over 2 hours at a liquid temperature of 50°C to 55°C. After the addition was complete, the mixture was stirred at a liquid temperature of 55°C to 60°C for 10 hours.

[0312] After stirring, the reaction mixture was cooled to a liquid temperature of 25°C to 30°C, extracted with n-hexane (100.0 g), and separated into an organic layer and an aqueous layer by chromatography. 20% hydrochloric acid (157.0 g) was added dropwise to the aqueous layer at a liquid temperature of 0°C to 10°C to make the aqueous layer acidic. The mixture was then extracted with n-hexane (150.0 g) and separated into an organic layer and an aqueous layer by chromatography. The obtained organic layer was washed twice with a 15% sodium chloride aqueous solution (500.0 g). The solvent was removed from the washed organic layer under reduced pressure to obtain (1,5,5-trimethyl-2-cyclopentenyl)acetic acid (6) (16.76 g: 0.099 mol, yield 99.6%, purity 93.2%).

[0313] The purity of (1,5,5-trimethyl-2-cyclopentenyl)acetic acid (6) prepared in this way allows the product (6) to be used without purification in subsequent processes.

[0314] The following are various spectral data of (1,5,5-trimethyl-2-cyclopentenyl)acetic acid (6) prepared in this way.

[0315] Nuclear magnetic resonance spectroscopy: 1 H-NMR (500MHz, CDCl3): δ0.94(3H,s),0.97(3H,s),1.02(3H,s),2.12(1H,dt,J=16.1,2.0Hz), 2.18(1H,dt,J=16.1,2.3Hz), 2.23(1H,d,J=13.8Hz), 2.36(1H,d,J=13.8Hz), 5.66(1H,dt,J=6.1,2.4Hz), 5.80(1H,dt,J=6.1,1.9Hz), 11.53(1H,br)ppm. 13 C-NMR (126MHz, CDCl3): δ19.65, 24.02, 24.37, 40.37, 44.13, 46.58, 49.70, 128.14, 138.44, 179.96ppm.

[0316] Mass spectrometry EI (70 eV): m / z 168 (M + ),153,135,109,93,91,79,67,55,41,27.

[0317] Infrared absorption spectrum (D-ATR): ν (cm) -1 )661,716,741,954,1137,1199,1235,1295,1374,1386,1409,1449,1706,2844,2966,3053.

[0318] Example 2-3

[0319] Preparation of (1,5,5-trimethyl-2-cyclopentenyl)acetic acid (6) (according to the aforementioned preparation process 2)

[0320] The crude product of ethyl (1,5,5-trimethyl-2-cyclopentenyl)acetate (2:R=Et) (9.81 g: 0.050 mol, purity 41.8%) was obtained by the same process as in Examples 1-1. Next, the crude product was subjected to the same process as in Examples 2-2. As a result, (1,5,5-trimethyl-2-cyclopentenyl)acetic acid (6) (8.09 g: 0.048 mol, yield 96.2%, purity 96.1%) was obtained. The purity of the (1,5,5-trimethyl-2-cyclopentenyl)acetic acid (6) thus prepared allows compound (6) to be used without further purification in subsequent processes.

[0321] The various spectral data of (1,5,5-trimethyl-2-cyclopentenyl)acetic acid (6) thus prepared are the same as those determined in Examples 2-2.

[0322] Furthermore, according to Examples 2-3, even when the purity of ethyl (1,5,5-trimethyl-2-cyclopentenyl)acetic acid (2:R=Et) is low, the purity of the resulting (1,5,5-trimethyl-2-cyclopentenyl)acetic acid (6) can be increased because an aqueous solution of sodium hydroxide, which can be extracted with alkali, is used in the hydrolysis process.

[0323] Examples 2-4

[0324] Preparation of 2-(1,5,5-trimethyl-2-cyclopentenyl)ethanol (5) (according to the aforementioned preparation process 2)

[0325]

[0326] The air in the reactor, equipped with a stirrer, condenser, and thermometer, was purged with nitrogen. Then, (1,5,5-trimethyl-2-cyclopentenyl)acetic acid (6) (33.64 g: 0.200 mol, purity: 96.1%) and tetrahydrofuran (THF) (300.0 g) obtained according to Examples 2-3 were added to the reactor, followed by cooling to a liquid temperature of -5°C to 0°C. A 70% by weight toluene solution (115.53 g: 0.400 mol) of sodium bis(2-methoxyethoxy)aluminum hydride (NaAlH2(OC2H4OCH3)2) was added dropwise to the reactor over 2 hours at a liquid temperature of 0°C to 5°C. After the addition was complete, the reaction mixture was stirred at a liquid temperature of 20°C to 25°C for 1 hour, and then further stirred at a liquid temperature of 55°C to 60°C for 6 hours. The reaction mixture was cooled to no more than 5°C, and then a 10% by weight aqueous solution of sodium hydroxide (320.0 g) was added dropwise to the reactor at a liquid temperature of 5°C to 15°C. After the addition was complete, the reaction mixture was stirred at a liquid temperature of 35°C to 40°C for 1 hour.

[0327] After stirring, the reaction mixture was separated into an organic layer and an aqueous layer. The obtained organic layer was washed twice with a 10% by weight aqueous solution of sodium chloride (200.0 g). The solvent was removed from the washed organic layer under reduced pressure to obtain 2-(1,5,5-trimethyl-2-cyclopentenyl)ethanol (5) (28.63 g: 0.186 mol, yield 92.8%, purity 87.8%). The purity of the 2-(1,5,5-trimethyl-2-cyclopentenyl)ethanol (5) thus prepared allows product (5) to be used without further purification in subsequent processes.

[0328] The various spectral data of the 2-(1,5,5-trimethyl-2-cyclopentenyl)ethanol (5) thus prepared are the same as those determined in Example 2-1.

[0329] Examples 2-5

[0330] Preparation of 2-(1,5,5-trimethyl-2-cyclopentenyl)ethyl acetate (3) (Both preparation processes 1 and 2 described above are conventional)

[0331]

[0332] The air in the reactor, equipped with a stirrer, condenser, and thermometer, was purged with nitrogen. Then, 2-(1,5,5-trimethyl-2-cyclopentenyl)ethanol (5) (30.85 g: 0.200 mol, purity 86.7%), pyridine (31.64 g: 0.400 mol), and tetrahydrofuran (THF) (230.0 g) obtained according to Examples 2-4 were added to the reactor, and the reactor was cooled to a liquid temperature of 5°C to 10°C. Acetic anhydride ((CH3CO)2O) (30.63 g: 0.300 mol) was added dropwise to the reactor over 1 hour at a liquid temperature of 10°C to 20°C. After the addition was complete, the reaction mixture was stirred over a liquid temperature of 20°C to 25°C for 1 hour, followed by stirring over a liquid temperature of 30°C to 35°C for 12 hours. The reaction mixture was cooled to no more than 10°C, and then water (150.0 g) was added dropwise to the reactor to quench the reaction. Diethyl ether (250.0 g) was added to the reaction mixture for extraction and layer separation to obtain an organic layer and an aqueous layer. The organic layer thus prepared was washed successively with 3% hydrochloric acid (250.0 g), 5% sodium bicarbonate (250.0 g), and 20% sodium chloride aqueous solution (200.0 g). The solvent was removed from the washed organic layer under reduced pressure, and the crude product was purified by vacuum distillation to obtain ethyl 2-(1,5,5-trimethyl-2-cyclopentenyl)ethyl acetate (3) (36.51 g: 0.186 mol, yield 93.0%, purity 93.4%).

[0333] The following are various spectral data of ethyl 2-(1,5,5-trimethyl-2-cyclopentenyl)acetate (3) prepared in this manner.

[0334] Nuclear magnetic resonance spectroscopy: 1 H-NMR (500MHz, CDCl3): δ0.88(3H,s),0.93(3H,s),0.94(3H,s),1.52-1.58(1H,m),1.66-1.71(1H,m),2.03(1H,s),2.11(2H,t,J=2.3H z), 4.07 (1H, ddd, J = 10.7, 9.6, 6.1Hz), 4.18 (1H, ddd, J = 10.7, 9.6, 5.7Hz), 5.54 (1H, dt, J = 6.2, 2.7Hz), 5.61 (1H, dt, J = 5.9, 2.6Hz) ppm. 13 C-NMR (126MHz, CDCl3): δ19.33,21.04,24.01,24.61,34.53,4,4.02,46.77,49.38,62.71,128.17,138.68,171.11ppm.

[0335] Mass spectrometry EI (70 eV): m / z 196 (M) + ),136,121,109,93,81,80,79,77,67,55,43,29.

[0336] Infrared absorption spectrum (D-ATR): ν (cm) -1 )716,961,1031,1053,1235,1387,1452,1743,2843,2872,2967,3051.

[0337] Comparative example

[0338] Comparative Example 1 below describes a method for preparing ethyl (1,5,5-trimethyl-2-cyclopentenyl) acetate (2:R=Et) from the aforementioned 3,4,4-trimethyl-2-cyclopentenyl-1-ol (8) using the Johnson-Clayson rearrangement reaction described in Non-Patent Document 3.

[0339] Comparative Example 1

[0340] Preparation of ethyl (1,5,5-trimethyl-2-cyclopentenyl) acetate (2:R=Et)

[0341]

[0342] The air in the reactor, equipped with a stirrer, condenser, distillation column, and thermometer, was purged with nitrogen. Then, 3,4,4-trimethyl-2-cyclopenten-1-ol (8) (12.62 g: 0.100 mol, 94.9% purity), triethyl orthoacetate (CH3C(OEt)3) (81.12 g: 0.500 mol), and propionic acid (C2H5COOH) (0.74 g: 0.010 mol) were added to the reactor. The mixture was then stirred at a liquid temperature of 140°C to 145°C for 38 hours, while refluxed ethanol was distilled off from the top of the fractionation column. After stirring, the reaction mixture was cooled to a liquid temperature of 20°C to 25°C. Excess triethyl orthoacetate was removed from the reaction mixture under reduced pressure, and the crude product was then purified by silica gel column chromatography to obtain ethyl (1,5,5-trimethyl-2-cyclopentenyl) acetate (2:R=Et) (5.95 g: 0.030 mol, yield 30.3%).

[0343] The ethyl (1,5,5-trimethyl-2-cyclopentenyl) acetate (2:R=Et) prepared in this way 1 The H-NMR nuclear magnetic resonance spectroscopy and mass spectrometry data are the same as those determined in Examples 1-1.

[0344] The yield of ethyl (1,5,5-trimethyl-2-cyclopentenyl) acetate (2:R=Et) obtained in Comparative Example 1 was 30.3%, which was lower than the yield of 49.7% in Example 1-1, lower than the yield of 47.8% in Example 1-2, lower than the yield of 43.9% in Example 1-3, and lower than the yield of 48.4% in Example 1-4.

Claims

1. A method for preparing ethyl 2-(1,5,5-trimethyl-2-cyclopentenyl)acetate (3) of formula (3): Where Ac represents the acetyl group. The method includes: The following haloacetal alkyl 3,4,4-trimethyl-2-cyclopentenyl acetals of general formula (1) are subjected to dehydrohalogenation in the presence of a base: Where R represents a straight-chain or branched alkyl group having 1 to 4 carbon atoms, and Y represents a halogen atom. A rearrangement reaction was then carried out to obtain a (1,5,5-trimethyl-2-cyclopentenyl) acetate compound of the following general formula (2): Where R is defined above, and The alkoxycarbonylmethyl group -CH2C(=O)OR of (1,5,5-trimethyl-2-cyclopentenyl)acetate compound (2) was subjected to a multi-step transformation to convert it into a 2-acetoxyethyl group -CH2CH2OAc, thereby obtaining 2-(1,5,5-trimethyl-2-cyclopentenyl)acetate (3).

2. The method of claim 1, wherein the multi-step conversion comprises a reduction reaction followed by an acetylation reaction.

3. The method of claim 1, wherein the multi-step conversion comprises a hydrolysis reaction, followed by a reduction reaction, and then an acetylation reaction.

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