JPH10195004A - Optically active alcohol and its production - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject now compound having a CF3 group on an asymmetric carbon and a branched alkyl chain at a terminal, easily producible and capable of imparting a large tilt angle, a high upper limit temperature in a dielectric phase and a low viscosity to a liquid crystal. SOLUTION: A compound of R-form or S-form of formula I [C* is an asymmetric carbon; (m)=0-5; (n)=1-5], e.g. R-(+)-1,1,1-trifluoro-5-methylhexan-2-ol. A compound of formula I is obtained by converting a compound of formula II (X is I, Br or Cl) to a Grignard reagent, reacting the resultant reagent with an alkali metal salt of trifluoroacetic acid to obtain a compound of formula III, reducing the product to obtain a compound of formula IV, reacting this product with a carboxylic anhydride to obtain a compound of formula V (COOR is a 2-6C alkyloxy), then asymmetrically hydrolyzing the obtained compound with lipase, subsequently bringing the reaction mixture to contact with an organic solvent compatible with water to precipitate the lipase, filtering the lipase and separating the objective compound from the filtrate.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel secondary optically active alcohol having a trifluoromethyl group on an asymmetric carbon and a branched alkyl chain at a terminal, and a method for producing the same.

[0002]

2. Description of the Related Art Optically active substances have hitherto been used in the fields of pharmaceuticals and agricultural chemicals, but have recently attracted attention as functional materials such as ferroelectric liquid crystals and organic nonlinear materials. For example, in the field of organic nonlinear materials, it is desirable that an asymmetric center exists in a molecule in order for the organic material to produce a second-order nonlinear optical effect (for example, Yamaguchi, Nakano, Fueno, Chemistry, 42 (11) ), 757 (1987)). Also,
In the field of ferroelectric liquid crystals, it is essential that liquid crystal molecules be optically active in order for liquid crystals to exhibit ferroelectricity
(For example, Jono, Fukuda, Journal of Synthetic Organic Chemistry, 47 (6), 5
68 (1989)).

In recent years, antiferroelectric liquid crystals have attracted much attention, but liquid crystal molecules need to be optically active compounds like ferroelectric liquid crystals. Conventionally, in such a field, as an optically active source, optically active 2-butanol,
Octanol, 2-methyl-1-butanol, amino acid derivatives and the like have been used. However, when such an optically active compound is used, the properties of the obtained material are limited.

[0004] Recently, in the field of ferroelectric liquid crystals, attempts have been made actively to synthesize ferroelectric liquid crystal compounds using the following alcohols substituted on asymmetric carbon with fluorine as an optically active source ( For example, JP-A-64-3154, JP-A-1-316339, 1-316367, 1-3316372,
2-225434, 2-229128). (1): CF ₃ C * H (OH) CH ₂ COOC ₂ H ₅ (2): CF ₃ C * H (OH) CH ₂ CH ₂ OC ₂ H ₅ (3): CF ₃ C * H (OH) CH ₂ CH ₂ CH ₂ OC ₂ H ₅ (4): CF ₃ C * H (OH) C ₆ H ₁₃ C (5): CF ₃ C * H (OH) C ₈ H ₁₇ (6): C ₂ F ₅ C * H (OH) C ₈ H ₁₇

[0005] Since ferroelectric liquid crystal compounds derived from these alcohols each have a trifluoromethyl group having a high electronegativity on asymmetric carbon, they give large spontaneous polarization and are relatively fast. Give response speed. Also, (4): CF ₃ C * H (OH) C ₆ H ₁₃ , (5): CF ₃ C * H (OH) C ₈ H ₁₇ , (6):
It has been recognized that liquid crystal compounds derived using C ₂ F ₅ C * H (OH) C ₈ H ₁₇ or the like often have an antiferroelectric phase, and as a very characteristic alcohol Attracting attention.

Further, the present inventors have developed CF ₃ C * H (OH) (CH ₂ ) _m O
The optically active alcohol represented by C _n H _{2n + 1} (where m is an integer of 2 to 7 and n is an integer of 1 to 4) has a high optical purity without using expensive trifluoroethyl ethyl acetate. A detailed study of new production methods for obtaining the desired optically active alcohols and liquid crystals derived from them will be carried out, and it will be possible to obtain extremely useful antiferroelectric liquid crystal compounds or ferrielectric liquid crystal compounds which have not been known before. (JP-A-5-65486 and JP-A-08-33555).

However, antiferroelectric liquid crystal compounds or ferrielectric liquid crystal compounds derived using the above-mentioned optically active alcohol have the following problems. (i) The tilt angle is small. (ii) The maximum temperature of the antiferroelectric phase or the ferrielectric phase is low. (iii) High viscosity. For this reason, an optically active alcohol capable of imparting a property capable of solving the above-mentioned problem to a liquid crystal is required.

[0008] Secondary optically active alcohols can be produced by various methods. From an economic viewpoint, using an optically active substance as a starting material is not economical because the raw material is expensive. Further, it can also be produced by a method using asymmetric synthesis. For example, when trying to obtain an optically active alcohol, it is conceivable to prepare a corresponding ketone body as a precursor and asymmetric reduction using an asymmetric reduction catalyst. However, according to this method, the asymmetric reduction catalyst is extremely expensive and a product with high optical purity is not always obtained, and only one of R and S optically active compounds is obtained.

Next, a method of asymmetric hydrolysis of a suitable ester which is a precursor of the optically active substance, for example, acetate, is considered. Effective asymmetric hydrolyzing agents include enzymes. Asymmetric hydrolysis of acetate by lipase has been proposed by Kitazume et al. (T. Kitazume
et al., J. Org. 52, 3211 (1987)), JP-A-2-282304.
No.).

According to this, the acetate represented by CF ₃ CH (OCOCH ₃ ) C _n H _{2n + 1} is asymmetrically hydrolyzed in a phosphate buffer by using lipase MY. However, the asymmetric recognition ability of lipase MY greatly depends on the chemical structure of the compound to be hydrolyzed, and as shown in Table 1 of the above-mentioned Kitazume et al. Purity varies greatly from 55-98ee%. This means that it is difficult to predict whether asymmetric hydrolysis of a target compound will be successful or not.In the end, it is necessary to carry out a reaction to determine whether the target alcohol can be obtained with high optical purity. Indicates that it is unknown.

Further, as a serious problem, depending on the type of the substituent on the asymmetric carbon, there is a case where no asymmetric recognition ability is exhibited. For example, lipase MY is CF ₃
C * H (OCOCH ₃ ) (CH ₂ ) ₅ shows extremely high asymmetric recognition ability in asymmetric hydrolysis of OC ₂ H ₅ . However, ester of secondary alcohol with methyl group substituted on asymmetric carbon CH ₃ CH (OCOCH ₃ )
C ₆ H ₁₃ has no asymmetric recognition.

In addition, as a method for producing a secondary optically active alcohol, there is a method in which a secondary racemic alcohol is subjected to asymmetric transesterification in the presence of an appropriate enzyme and optically resolved. For example, there is an asymmetric transesterification reaction using lipase (derived from pig pancreas) in an organic solvent (AMKlibano
v et al., J. Am. Chem. Soc. 1985, 106, 7072). However, a lipase having high activity and high enantioselectivity has not been known so far. In addition, the optical resolution by asymmetric hydrolysis and asymmetric transesterification using an enzyme is R-form,
There is an advantage that both S-forms can be easily obtained.

[0013]

SUMMARY OF THE INVENTION The present invention has been made in view of the above situation, and has a trifluoromethyl group on an asymmetric carbon and a branched alkyl chain at a terminal. It is intended to provide a novel secondary optically active alcohol and an effective production method thereof.

That is, the present invention relates to an optically active alcohol which is an R-form or an S-form represented by the following general formula (1). General formula (1): CF ₃ C * H (OH) (CH ₂ ) _m CH (C _n H _{2n + 1} ) ₂ (where C * is an asymmetric carbon, m is an integer of 0 to 5, and n is 1-5
Is an integer. In the present invention, preferred compounds are optically active alcohols wherein m is 0 to 4 in the general formula (1), and n is 1 to 4.
3 is an optically active alcohol.

The present invention also provides a process for producing an R- or S-form optically active alcohol represented by the following general formula (1), which comprises the following steps (1) to (4): It is a manufacturing method of. General formula (1): CF ₃ C * H (OH) (CH ₂ ) _m CH (C _n H _{2n + 1} ) ₂ (where C * is an asymmetric carbon, m is an integer of 0 to 5, and n is 1-5
Is an integer. Step (1): General formula (2): X (CH ₂ ) _m CH (C _n H _{2n + 1} ) ₂ (where m and n are the same as in general formula (1), and X is a halogen other than fluorine) After converting a halogen compound represented by an atom) into a Grignard reagent, the general formula (3): CF ₃ COOM ¹ (M ¹ in the formula is
Li, Na, or K) or the general formula (4): (CF ₃
COO) ^₂ M ₂ (M ₂ in the formula is reacted Mg, a metal trifluoroacetate represented by indicating one of Ca), the general formula _{(5): CF 3 CO (} CH 2) m CH ( C _n H _{2n + 1} ) ₂ (wherein m is the same as in the general formula (1)). Step (2): reducing the ketone of the general formula (5), (6): CF ₃ CH (OH) (CH ₂ ) _m CH (C _n H _{2n + 1} ) ₂ (wherein
m and n are the same as in the general formula (1)), a step of producing a racemic alcohol represented by the general formula (1), and step (3): reacting the alcohol of the general formula (6) with a carboxylic acid halide or a carboxylic anhydride. And an ester represented by the general formula (7): CF ₃ CH (OCOR) (CH ₂ ) _m CH (C _n H _{2n + 1} ) ₂ (wherein COR represents an alkyloxy group having 2 to 6 carbon atoms) Step (4): The ester of the general formula (7) is subjected to an asymmetric hydrolysis reaction with a lipase, and after the reaction is completed, the reaction solution is brought into contact with an organic solvent compatible with water, whereby the lipase is converted. A step of recovering lipase by precipitation and filtration, and separating optically active alcohol and optically active ester from the filtrate from which lipase has been removed.

In the present production method, in the step (1), it is preferable to use a metal trifluoroacetate to be reacted with a Grignard reagent as a tetrahydrofuran solution. In the step (2), it is preferable to use an aqueous solution of NaBH ₄ containing sodium hydroxide as a reducing agent for the ketone. This reduction reaction is preferably carried out at a temperature of from 20 to 40 ° C. In the step (3), the carboxylic acid halide or carboxylic anhydride includes acetic chloride, propionic chloride, butyric chloride, acetic anhydride and propionic anhydride. This step is performed at normal temperature
It is preferably carried out at 60-90 ° C.

The lipase used in the step (4) is preferably derived from pig pancreas, and particularly preferably lipase MY. This lipase MY is, for example, commercially available from Meito Sangyo Co., Ltd. and can be easily obtained. In the step (4), the asymmetric hydrolysis reaction with lipase is carried out at 20 to 40 ° C., and the amount of water used is desirably 20 to 50 times mol of the ester.

Further, in the step (4), the reaction solution after the asymmetric hydrolysis reaction with the lipase is brought into contact with an organic solvent in an amount of 5 to 20 times the amount of water used for the asymmetric hydrolysis to thereby reduce the lipase. The lipase is precipitated, and the precipitated lipase is collected by filtration, dried under reduced pressure, and can be suitably reused, so that the optically active alcohol of the present invention can be produced more economically. It is preferable that the organic solvent used at this time is selected from the group consisting of acetone, methanol, ethanol and tetrahydrofuran. On the other hand, the method of separating the optically active alcohol and the optically active ester obtained in this step (4) from the mixture is not particularly limited, but is usually by distillation. The separated optically active ester can be easily converted to an optically active alcohol by a known hydrolysis reaction.

[0019]

Industrial Applicability The present invention provides a novel secondary optically active alcohol having a trifluoromethyl group on an asymmetric carbon and a branched alkyl chain at the terminal, and provides an economical and convenient method for producing them. is there.

[0020]

Next, the present invention will be described in more detail by way of examples, but the present invention is not limited to these examples. Example 1 (general formula (1): m = 2, n = 1 (E1))
Production of (+)-1,1,1-trifluoro-5-methylhexane-2-ol.

(1) Synthesis of 1,1,1-trifluoro-5-methylhexane-2-ol 6.5 g (270 mmol) of metallic magnesium was placed in a round-bottomed flask, and after purging with nitrogen, dried tetrahydrofuran 100
ml (milliliter) was added. 1-bromo-3-methylbutane 16.6g
(110 mmol) dissolved in 100 ml of dry tetrahydrofuran was added dropwise so that the reaction temperature was 40 ° C. or lower. After aging for 1 hour, 200 g (280 mmol; 35% tetrahydrofuran solution) of magnesium bis (trifluoroacetic acid) was added dropwise so that the reaction temperature became 50 ° C. or less.
The reaction was performed at 50 ° C. for 2 hours.

After completion of the reaction, 150 ml of 6N hydrochloric acid was added dropwise, and the mixture was stirred at room temperature for 2 hours to separate an organic layer. To this, 28 g of 12% NaBH ₄ (aqueous NaOH solution) was slowly added dropwise.
After stirring at room temperature for 3 hours, water was added, followed by extraction with ether. The ether layer was washed with 6N hydrochloric acid, washed with water until almost neutral, and further washed with saturated saline. The ether layer was dried over anhydrous sodium sulfate, and ether was distilled off to obtain 25 g of a crude product. This was purified by distillation (20 Torr, 68 ° C.). Yield 9.5 g (purity by gas chromatography analysis (GC purity) 90%).

(2) 1,1,1-trifluoro-2-acetoxy-
Synthesis of 5-methylhexane. 1,1,1-trifluoro-5-methylhexane-2- obtained in (1)
To 6.5 g (38 mmol) of all, 10 g (98 mmol) of acetic anhydride and 10 g (130 mmol) of pyridine were added, followed by stirring at room temperature for 30 hours. After adding 10 ml of water and stirring for 10 hours, water was further added and extracted with ether. The ether layer was washed with 6N hydrochloric acid, washed with water until almost neutral, and further washed with saturated saline. After the ether layer was dried over anhydrous sodium sulfate, the ether was distilled off to obtain 14.8 g of a crude product. This was purified by distillation (20 Torr, 65
° C). Yield 6.6 g (GC purity 98%).

(3) Production of R-(+)-1,1,1-trifluoro-5-methylhexane-2-ol To 4.7 g (22 mmol) of the acetylated product obtained in (2), 30 g of water
And 8.2 g of Lipase MY (manufactured by Meito Sangyo Co., Ltd.), and the mixture was stirred at room temperature for 8 hours. Then add 150 ml of acetone 1
Stirred for hours. After the precipitated lipase was separated by filtration, acetone was distilled off. To this was added water and extracted with ether. The ether layer was washed several times with water, and further washed with saturated saline. After the ether layer was dried over anhydrous sodium sulfate, the ether was distilled off to obtain 3.1 g of a crude product.

This was purified by silica gel column chromatography to obtain R-(+)-1,1,1-trifluoro-5-methylhexane-2-ol and S-(-)-1,1,1-triol. Separated into fluoro-2-acetoxy-5-methylhexane. The yield of the R-(+) form was 1.0 g. S-(-)-1,1,1-trifluoro-5-methylhexane-2-ol is S-(-)-1,1,1-trifluoro-2-acetoxy-5-methylhexane. It is easily obtained by hydrolysis.

Table 1 shows the NMR data of the R-(+) form obtained above.
The specific rotation and optical purity are shown in Table 3. The specific rotation and the optical purity were determined as follows. The specific rotation is
The measurement was performed using a polarimeter using chloroform as a solvent. The optical purity was determined by converting the R-(+)-form optically active alcohol obtained in the above (3) to acetate with pyridine / acetic anhydride. The obtained acetate was analyzed with a gas chromatograph for analyzing an optically active substance (CP Cyclodex β236M).
Purity was determined from the peak area ratio of the two enantiomers.

Example 2 (general formula (1): m = 3, n = 1
(E2)) Production of R-(+)-1,1,1-trifluoro-6-methylheptan-2-ol. Example 1 was repeated except that 1-bromo-4-methylpentane was used instead of 1-bromo-3-methylbutane.
The target product was produced in exactly the same manner as described above. Example 3 (general formula (1): m = 4, n = 1 (E3))
Preparation of (+)-1,1,1-trifluoro-7-methyloctan-2-ol. Example 1 was repeated except that 1-bromo-5-methylhexane was used in place of 1-bromo-3-methylbutane.
The target product was produced in exactly the same manner as described above.

Example 4 (general formula (1): m = 0, n = 2
(E4)) Production of R-(+)-1,1,1-trifluoro-3-ethylpentan-2-ol. A target product was produced in the same manner as in Example 1 except that 3-bromopentane was used instead of 1-bromo-3-methylbutane. Example 5 (general formula (1): m = 0, n = 3 (E5))
Production of (+)-1,1,1-trifluoro-3-propylhexan-2-ol. A target compound was produced in exactly the same manner as in Example 1 except that 4-bromoheptane was used instead of 1-bromo-3-methylbutane.

Example 6 (general formula (1): m = 1, n = 1
(E6)) Production of R-(+)-1,1,1-trifluoro-4-methylpentan-2-ol. In Example 1, 1-bromo-2-methylpropane was used in place of 1-bumol-3-methylbutane, and the treatment was carried out in exactly the same manner as in Example 1 up to the asymmetric hydrolysis step (3). R-(+)-1,1,1-trifluoro-4-methylpentan-2-ol and S-(-)-1,1,1-trifluoro- obtained by asymmetric hydrolysis
The boiling point was very close to that of 2-acetoxy-4-methylpentane, and separation by distillation was difficult. Therefore, the target product was obtained as follows.

R-(+)-1,1,1-trifluoro-4-methylpentan-2-ol and S-(-)-1,1,1-trifluoro-2-acetoxy-4-methylpentane Octanoic acid chloride was added to the mixture to give R-(+)-1,1,1-trifluoro-4-methylpentan-2-ol as R-(+)-1,1,1-trifluoro -2-octanoyloxy-4-methylpentane. afterwards,
S-(-)-1,1,1-trifluoro-2-acetoxy-
4-Methylpentane was distilled off. To the remaining R-(+)-1,1,1-trifluoro-2-octanoyloxy-4-methylpentane, add water, ethylene glycol, potassium hydroxide,
Hydrolysis produced the target product.

Example 7 (general formula (1): m = 1, n = 2
(E7)) Production of R-(+)-1,1,1-trifluoro-4-ethylhexane-2-ol. A target compound was produced in the same manner as in Example 1 except that 1-bromo-2-ethylbutane was used instead of 1-bromo-3-methylbutane. Example 8 (general formula (1): m = 1, n = 3 (E8))
Preparation of (+)-1,1,1-trifluoro-4-propylheptane-2-ol. A target compound was produced in the same manner as in Example 1 except that 1-bromo-2-propylpentane was used instead of 1-bromo-3-methylbutane.

Example 9 (general formula (1): m = 2, n = 2
(E9)) Production of R-(+)-1,1,1-trifluoro-5-ethylheptane-2-ol. Example 1 was repeated except that 1-bromo-2-ethylpentane was used in place of 1-bromo-3-methylbutane.
The target product was produced in exactly the same manner as described above. Example 10 (general formula (1): m = 3, n = 2 (E10))
Preparation of (+)-1,1,1-trifluoro-6-ethyloctan-2-ol. Example 1 was repeated except that 1-bromo-4-ethylhexane was used instead of 1-bromo-3-methylbutane.
The target product was produced in exactly the same manner as described above.

Example 11 (general formula (1): m = 4, n = 2
(E11)) Production of R-(+)-1,1,1-trifluoro-7-ethylnonan-2-ol. Example 1 Example 1 was repeated except that 1-bromo-5-ethylheptane was used in place of 1-bromo-3-methylbutane.
The target product was produced in exactly the same manner as described above. Tables 1 and 2 show NMR data of the R-(+) form of the target compound obtained in Examples 1 to 11. Table 3 shows the results of measuring the specific rotation and the optical purity in the same manner as in Example 1.

[0034]

Table 1 Example Compounds and chemical shifts (ppm) No Proton number 1 2 3,4,56 1 CF ₃ C * H (OH) (CH ₂ ) ₂ CH (CH ₃ ) ₂ 3.8 2.0 1.2-1.8 0.9 (E1) 1 2 3 4 6 2 CF ₃ C * H (OH) (CH ₂ ) ₃ CH (CH ₃ ) ₂ 3.9 2.0 1.1-1.9 0.9 (E2) 1 2 3 4 6 3 CF ₃ C * H (OH ) (CH ₂ ) ₄ CH (CH ₃ ) ₂ 3.9 2.0 1.1-1.8 0.9 (E3) 1 2 3 4 6 4 CF ₃ C * H (OH) CH (CH ₂ CH ₃ ) ₂ 4.0 2.0 1.2-1.8 0.9 ( E4) 1 2 4 5 6 5 CF ₃ C * H (OH) CH ((CH ₂ ) ₂ CH ₃ ) ₂ 4.0 2.0 1.2-1.8 0.9 (E5) 1 2 4 5 6 6 CF ₃ C * H (OH) CH ₂ CH (CH ₃ ) ₂ 4.0 1.9 1.4-1.9 1.0 (E6) 1 2 3 4 6 7 CF ₃ C * H (OH) CH ₂ CH (CH ₂ CH ₃ ) ₂ 4.0 1.9 1.2-1.7 0.9 (E7) 1 2 3 4 5 6

[0035]

[Table 2] Example Compound and chemical shift (ppm) No Proton number 1 2 3,4,5 68 CF ₃ C * H (OH) CH ₂ CH ((CH ₂ ) ₂ CH ₃ ) ₂ 4.0 1.9 1.2- 1.7 0.9 (E8) 1 2 3 4 5 6 9 CF ₃ C * H (OH) (CH ₂ ) ₂ CH (CH ₂ CH ₃ ) ₂ 3.9 1.9 1.1-1.8 0.9 (E9) 1 2 3 4 5 6 10 CF ₃ C * H (OH) (CH ₂ ) ₃ CH (CH ₂ CH ₃ ) ₂ 3.9 2.0 1.1-1.8 0.9 (E11) 1 2 3 4 5 6 11 CF ₃ C * H (OH) (CH ₂ ) ₄ CH (CH ₂ CH ₃ ) ₂ 3.9 2.0 1.1-1.8 0.9 (E11) 1 2 3 4 5 6

[0036]

[Table 3] Example No. Chemical structural formula Optical purity Specific rotation ^{* 1} 1 (E1) CF ₃ C * H (OH) (CH ₂ ) ₂ CH (CH ₃ ) ₂ 92% ee + 25.8 ° 2 (E2 ) CF ₃ C * H (OH) (CH ₂ ) ₃ CH (CH ₃ ) ₂ 96% ee + 25.0 ° 3 (E3) CF ₃ C * H (OH) (CH ₂ ) ₄ CH (CH ₃ ) ₂ 90% ee + 21.8 ° 4 (E4) CF ₃ C * H (OH) CH (C ₂ H ₅ ) ₂ 89% ee + 18.9 ° 5 (E5) CF ₃ C * H (OH) CH (C ₃ H ₇ ) ₂ 78% ee + 20.5 ° 6 (E6) CF ₃ C * H (OH) CH ₂ CH (CH ₃ ) ₂ 92% ee + 30.4 ° 7 (E7) CF ₃ C * H (OH) CH ₂ CH (C ₂ H ₅ ) ₂ 92% ee + 21.8 ° 8 (E8) CF ₃ C * H (OH) CH ₂ CH (C ₃ H ₇ ) ₂ 97% ee + 39.7 ° 9 (E9) CF ₃ C * H (OH) (CH ₂ ) ₂ CH (C ₂ H ₅ ) ₂ 90% ee + 23.8 ° 10 (E12) CF ₃ C * H (OH) (CH ₂ ) ₃ CH (C ₂ H ₅ ) ₂ 82% ee + 20.4 ° 11 (E13) CF ₃ C * H (OH) (CH ₂ ) ₄ CH (C ₂ H ₅ ) ₂ 76% ee + 17.0 ° * 1: Measured at 29 ° C with sodium D line.

Claims (10)

[Claims] 1. An optically active alcohol which is an R-form or an S-form represented by the following general formula (1). General formula (1): CF ₃ C * H (OH) (CH ₂ ) _m CH (C _n H _{2n + 1} ) ₂ (where C * is an asymmetric carbon, m is an integer of 0 to 5, and n is 1-5
Is an integer. ) 2. The optically active alcohol according to claim 1, wherein m is 0 to 4 in the general formula (1). 3. The optically active alcohol according to claim 1, wherein n is 1 to 3 in the general formula (1). 4. A method for producing an R- or S-form optically active alcohol represented by the following general formula (1), comprising:
A method for producing an optically active alcohol, comprising (1) to (4). General formula (1): CF ₃ C * H (OH) (CH ₂ ) _m CH (C _n H _{2n + 1} ) ₂ (where C * is an asymmetric carbon, m is an integer of 0 to 5, and n is 1-5
Is an integer. Step (1): General formula (2): X (CH ₂ ) _m CH (C _n H _{2n + 1} ) ₂ (where m and n are the same as in general formula (1), and X is a halogen other than fluorine) After converting a halogen compound represented by an atom) into a Grignard reagent, the general formula (3): CF ₃ COOM ¹ (M ¹ in the formula is
Li, Na, or K) or the general formula (4): (CF ₃
COO) ^₂ M ₂ (M ₂ in the formula is reacted Mg, a metal trifluoroacetate represented by indicating one of Ca), the general formula _{(5): CF 3 CO (} CH 2) m CH ( C _n H _{2n + 1} ) ₂ (wherein m is the same as in the general formula (1)). Step (2): reducing the ketone of the general formula (5), (6): CF ₃ CH (OH) (CH ₂ ) _m CH (C _n H _{2n + 1} ) ₂ (wherein
m and n are the same as in the general formula (1)), a step of producing a racemic alcohol represented by the general formula (1), and step (3): reacting the alcohol of the general formula (6) with a carboxylic acid halide or a carboxylic anhydride. And an ester represented by the general formula (7): CF ₃ CH (OCOR) (CH ₂ ) _m CH (C _n H _{2n + 1} ) ₂ (wherein COR represents an alkyloxy group having 2 to 6 carbon atoms) Step (4): The ester of the general formula (7) is subjected to an asymmetric hydrolysis reaction with a lipase, and after the reaction is completed, the reaction solution is brought into contact with an organic solvent compatible with water, whereby the lipase is converted. A step of recovering lipase by precipitation and filtration, and separating optically active alcohol and optically active ester from the filtrate from which lipase has been removed. 5. The process for producing an optically active alcohol according to claim 4, wherein in the step (1), a metal trifluoroacetate to be reacted with a Grignard reagent is used as a solution in tetrahydrofuran. 6. The method for producing an optically active alcohol according to claim ₄ , wherein in the step (2), an aqueous NaBH ₄ solution containing sodium hydroxide is used as a ketone reducing agent. 7. The method for producing an optically active alcohol according to claim 4, wherein in the step (4), the asymmetric hydrolysis reaction with lipase is carried out at 20 to 40 ° C. 8. The process for producing an optically active alcohol according to claim 4, wherein in the step (4), the amount of water used in the asymmetric hydrolysis reaction with lipase is 20 to 50 times mol of the ester. 9. In the step (4), the reaction solution after the asymmetric hydrolysis reaction with lipase is brought into contact with an organic solvent in an amount of 5 to 20 times the amount of water used for the asymmetric hydrolysis to thereby reduce lipase. The method for producing an optically active alcohol according to claim 4, wherein the lipase is precipitated, recovered by filtration, dried under reduced pressure, and reused in the step (4). 10. The method for producing an optically active alcohol according to claim 4, wherein said organic solvent is at least one selected from the group consisting of acetone, methanol, ethanol and tetrahydrofuran.