JPH0959220A - Syn-(2s,3r)-7-ethoxy-3-methoxyheptane derivative and liquid crystal display element - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject new compound which is an antiferrodielectric conductive compound exhibiting a chiral smectic CA phase having a fast responding property, a wide visual field angle and a three-dimensionally stable state, and useful as a material for large face plate liquid crystal displays. SOLUTION: A compound of formula I (R is a 6-14C linear alkyl). For example, syn-(2S,3R)-2- 4-[4-(4-n-decylphenyl)benzoyloxy]benzoyloxy}-7-ethoxy-3- methoxyl-1,1,1-trifluoroheptane. The compound of formula I is obtained by reacting a compound of formula II with syn-(2S,3R)-2-(4-hydroxybenzoyloxy)-7- ethoxy-3-methoxy-1,1,1-trifluoroheptane in the presence of a dehydrative condensing agent and a catalyst.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a novel liquid crystal compound syn- (2S, 3R) -7-ethoxy-3-methoxyheptane derivative and a liquid crystal display device using the same. More specifically, the present invention is the above-described compound which is an antiferroelectric liquid crystal compound exhibiting a chiral smectic C _A phase (hereinafter referred to as S _CA ☆) having a fast response, a wide viewing angle and a tristable state. And a liquid crystal display device using the same.

[0002]

BACKGROUND OF THE INVENTION Antiferroelectric liquid crystal compounds exhibit three stable states with respect to an applied electric field, and since steep threshold values and double hysteresis curves exist, multiplex driving is possible, and high-speed response and wide field of view It has corners and is expected as a large screen liquid crystal display material, a wall-mounted television material, and the like. However, since have been published in many literature to date (R) -l, l, l antiferroelectric liquid crystal compound comprising a trifluoromethyl nonane derivative present to a high temperature range from room temperature S _CA ☆, room temperature It is inferior to operability and is not put to practical use as a large screen liquid crystal display material and a wall-mounted television material. Accordingly, there is a need for antiferroelectric liquid crystal compounds comprising novel optically active compounds.

[0003]

Therefore, the present invention is different from the conventionally known antiferroelectric liquid crystal compound consisting of (R) form of one asymmetric carbon atom, in which two adjacent ones are separated. Novel antiferroelectric liquid crystal compound comprising syn form (2S, 3R) type having asymmetric carbon atoms, which alone exhibits high-speed response and wide viewing angle (high tilt angle), particularly at around room temperature S
An antiferroelectric liquid crystal compound having _CA * is provided.

[0004]

SUMMARY OF THE INVENTION The present invention is a novel compound represented by the formula (1)

[0005]

[Chemical formula 2]

(Wherein, R is a linear C 6-14 alkyl
Represents a kill group. Syn- (2S, 3R) indicated by)
-2- {4- [4- (4) -Alkylphenyl) benzoi
Ruoxy] benzoyloxy} -7-ethoxy-3-methyl
Anti-strong which is Toxi-1,1,1-trifluoroheptane
Dielectric liquid crystal compounds (hereinafter referred to as the present compound) and
And a liquid crystal display device using the compound of the present invention.

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION

(Inventive compound) The inventive compound is as represented by the formula (1), wherein the alkyl group represented by R has 6 carbon atoms
To 14 linear alkyl groups, ie, n-hexyl group, n-heptyl group, n-octyl group, n-nonyl group,
n-decyl group, n-undecyl group, n-dodecyl group, n
-Tridecyl and n-tetradecyl are mentioned,
Among them, useful alkyl groups are linear alkyl groups having 8 to 12 carbon atoms.

Preferred specific examples of the compound of the present invention are as follows:
syn- (2S, 3R) -2- {4- [4- (4) -N-
Octylphenyl) Benzoyloxy] benzoyloxy
7-Ethoxy-3-methoxy-1,1,1-tri
Fluoroheptane, syn- (2S, 3R) -2- {4
-[4- (4 -N-nonylphenyl) benzoyl ester
ベ ン ゾ イ ル] Benzoyloxy} -7-ethoxy-3-methoxy
-1,1,1-trifluoroheptane, syn-(2
S, 3R) -2- {4- [4- (4) -N-decyl pheny
Le) Benzoyloxy] Benzoyloxy} -7-Eto
Xy-3-methoxy-1,1,1-trifluorohepta
, Syn- (2S, 3R) -2- {4- [4- (4) -
n-Undecylphenyl) benzoyloxy] benzoi
Ruoxy} -7-ethoxy-3-methoxy-1,1,1
-Trifluoroheptane, and syn-(2S, 3
R) -2- {4- [4- (4) -N-dodecylphenyl)
Benzoyloxy] benzoyloxy} -7-ethoxy
-3-Methoxy-1,1,1-trifluoroheptane etc.
Can be mentioned.

[Compounds of the Invention: syn- (2S, 3R)
-2- {4- [4- (4) -Alkylphenyl) benzoi
Ruoxy] benzoyloxy} -7-ethoxy-3-methyl
Process for producing Toxi-1,1,1-trifluoroheptane
Method] The compound of the present invention is represented by the formula (2)

[0010]

[Chemical formula 3]

(Wherein R represents a linear alkyl group of 6 to 14 carbons), the novel compound syn- (2S, 3R) -2- (4-hydroxybenzoyl) in an organic solvent Oxy) -7-ethoxy-3-methoxy-
1,1,1-trifluoroheptane (hereinafter referred to as a raw material compound) and 4- (4-n-alkylphenyl) benzoic acid using dicyclohexylcarbodiimide as a dehydration condensation agent, and N, N- as a catalyst It can be easily produced by reaction using an organic base such as dimethyl-4-aminopyridine. The organic solvent is preferably a chlorinated solvent such as methylene chloride or chloroform. The amount of the organic solvent used is 20 to 20 mol based on 1 mol of the starting compound.
40 liters is preferred. If the amount is less than 20 liters, 4- (4-n-alkylphenyl) benzoic acid may be difficult to dissolve, which may cause a decrease in the yield, and if it exceeds 40 liters, it is not economical. Starting compounds and 4-
The feed ratio with (4-n-alkylphenyl) benzoic acid is preferably 1.1 to 1.3 mol based on 1 mol of the raw material compound. If it is less than 1.1 mol, the yield may be lowered, and if it is more than 1.3 mol, it is not economical.

The mixing ratio of the starting compound to the N, N-dimethylaminopyridine is, based on 1 mol of the starting compound,
0.4 to 0.8 mol is preferable. If it is less than 0.4 mol, dehydration time will be long, which may lead to a decrease in yield, 0.8
It is not economical if it exceeds the mole. Starting compounds and 4-
(4-n-alkylphenyl) benzoic acid and N, N, N
Add methylene chloride to dimethylaminopyridine and formulate a homogeneous solution with stirring at room temperature. Then add dicyclohexyl carbodiimide to the above solution,
Make a homogeneous solution with stirring. The feed amount of dicyclohexylcarbodiimide to the above solution is preferably 1.3 to 1.7 mol based on 1 mol of the starting compound. 1.3
If it is less than the mole, the dehydration condensation reaction may be insufficient, which may lead to a decrease in the yield, and if it exceeds 1.7 moles, it is not economical. After the dicyclohexyl carbodiimide is completely fed, the reaction is carried out at room temperature with stirring. The reaction time is preferably 25 to 35 hours per mole of the starting compound. 25
If it is less than time, the yield may be lowered, and if it is more than 35 hours, it is not economical. The reaction temperature is preferably room temperature.

After completion of the reaction, precipitated dicyclohexyl urine
The white crystals of the pigment are removed by filtration, and the filtrate is washed with 1 N hydrochloric acid.
After cleaning, 10 Washed with aqueous sodium bicarbonate solution
Then, wash with water and add anhydrous magnesium sulfate to remove water
After removal of the solvent under reduced pressure, the syrupy residue is removed.
Get After dissolving the obtained residue with hot n-hexane,
Cooling crystallization gives white crude crystals. Then the crude obtained
The crystals are purified by liquid chromatography to give a colorless clear liquid
-(2S, 3R) -2 as a compound of the present invention
-{4- [4- (4) -Alkylphenyl) benzoyl io
Xy] benzoyloxy} -7-ethoxy-3-methoxy
1, -1,1-trifluoroheptane is obtained.

Further, since this reaction is irrelevant to the configuration of the two asymmetric carbon atoms of the starting compound, the optically active asymmetric center does not change, and it is in the syn form (2S, 3R). . Furthermore, in the identification example of Example 1 described later, it has been confirmed that the compound of the present invention is a syn isomer (2S, 3R). As a result of measuring the phase transition temperature of the compound of the present invention thus obtained, the temperature range of S _CA ☆ is

[0015]

[Chemical formula 4]

Thus, it is confirmed that the compound of the present invention is an antiferroelectric liquid crystal compound in which _SCA * contains around room temperature.
Furthermore, a liquid crystal display element made of the compound of the present invention is prepared, and using the display element, one dark state and two bright states are obtained by the change in transmitted light amount with respect to the change in applied voltage at 25 ° C.
A steady state double hysteresis curve is obtained. As a result of measuring the performance of the display element based on this, high-speed response,
The low threshold value and the high tilt angle confirm that the compound of the present invention is an excellent antiferroelectric liquid crystal compound which forms a liquid crystal display element operable at room temperature. Note that
The raw material compounds are novel compounds and can be obtained by the following reaction steps.

[0017]

[Chemical formula 5]

[0018]

EXAMPLES The present invention will be specifically described by way of reference examples and examples. Reference Examples 1 to 5 are (S) -N- (2-
Hydroxy-3,3,3-trifluoropropionyl)
The preparation example from pyrrolidine (starting material compound) to the starting compound, Example 1 is a preparation example of the compound of the present invention, and Test Example 1 is a test example showing the usefulness of the compound of the present invention.

Reference Example 1 [Starting Material Compound: (S) -N-
(Preparation of 2-hydroxy-3,3,3-trifluoropropionyl) pyrrolidine In a three-necked round bottom flask equipped with a thermometer, a stirrer and a reflux condenser, 25.8 g (179 mmol) of (S) -trifluorolactic acid , 520 ml of methanol and 270 ml of concentrated sulfuric acid
The mixture was heated to reflux with stirring. During reflux, ¹⁹ FNM
As a result of refluxing for 12 hours while tracking a lactic acid peak in R spectrum, it was confirmed that the lactic acid in the reaction solution was gone.
Then, the reaction solution is adjusted to pH with a saturated aqueous solution of sodium hydrogen carbonate
The extract is extracted with ether and the extract is washed with water, anhydrous magnesium sulfate is added to remove water, the extract is concentrated under reduced pressure, and the remaining syrupy residue is distilled under reduced pressure, Colorless and transparent liquid product [yield 26.9 g
(170 mmol) yield 95%] was obtained.

¹ H NMR spectrum of this product, ¹⁹ F
NMR spectrum, 1R absorption spectrum and MS spectrum were measured. Also, the product is (S) -2-hydroxy-3, which is independent of the configuration of the carbon atom at position 2 of this product and optical inversion does not occur.
It was confirmed to be 3,3-trifluoropropionic acid methyl ester.

Next, attach a Liebig condenser to a branch of a Claisen flask with a thermometer, a stirrer, and a dropping funnel, attach a methyl alcohol recovery bottle at its outlet, and connect the outlet to an aspirator, as described above. Obtained by (S) -2-hydroxy-
26.1 g (165 mmol) of 3,3,3-trifluoropropionic acid methyl ester and 12.8 g of pyrrolidine
(180 mmol) and 0.7 mmol of concentrated sulfuric acid were introduced and reacted at 200 mmHg.times.60.degree. C. The methyl alcohol vapor generated was continuously sent to a Liebig condenser to recover methyl alcohol. Confirm that generation of methyl alcohol vapor has disappeared, and stop heating,
After cooling to room temperature, the pressure was returned to normal pressure to complete the reaction.
Next, the light brown solid formed is taken out, washed with water, dissolved by adding hot n-hexane, and then crystallized by cooling to give a white needle-like crystalline product [yield 27.6 g (14
0 mmol) yield 85%] was obtained.

¹ H NMR spectrum of this product, ¹⁹ F
The results of measurement of NMR spectrum, 1R absorption spectrum, and MS spectrum are as follows, and are independent of the configuration of the asymmetric carbon atom of this product, and optical inversion does not occur. Was confirmed to be the starting compound (S) -N- (2-hydroxy-3,3,3-triculopropionyl) pyrrolidine. ¹ H NMR spectrum (CDCl ₂ ) 1.53 to 2.37 ppm (4 H, m), 3.21 to
3.88 ppm (4H, m), 4.14 ppm (1 H,
br), 4.58 (1 H, q) ¹⁹ F NMR spectrum (from ext. CF ₃ C
OOH) −4.2 ppm (d, J = 6.0) 1R absorption spectrum (neat) 1,640 cm ⁻¹ (CO), 3,330 cm ⁻¹ (OH) MS spectrum m / z 197 (M ⁺ )

Reference Example 2 ( Preparation of Grignard reagent: 4-ethoxybutyl magnesium bromide) 40.0 g of tetrahydrofuran (55 g) in a four-necked round-bottomed flask equipped with a thermometer, a stirrer, a reflux condenser, and a dropping funnel.
6 mmol), 28.2 g (612 mmol) of ethyl alcohol and 5.2 g of para-toluenesulfonic acid monohydrate
(29 mmol) was added and immersed in a hot water bath. Then, after refluxing at 80 ° C. for 6 hours, concentration was performed under reduced pressure to obtain a syrupy residue. To this residue is added 620 ml of water, followed by extraction with ether, extraction and addition of anhydrous magnesium sulfate to remove water, and then the solvent is distilled off under reduced pressure to give colorless clear liquid 4-ethoxybutanol [yield 59.0 g ( 500 mmol) yield 90%] was obtained.

Next, 57.2 g (485 mmol) of 4-ethoxybutanol obtained above and methylene chloride 1, 4 were obtained in a three-necked flask equipped with a thermometer, a stirrer and a dropping funnel.
50 L was added and immersed in an ice water bath and adjusted to 0 ° C. Then add triphenylphosphine 126.6 to the dropping funnel.
Put g (485 millimoles) and 485 liters of methylene chloride,
A completely homogeneous solution was prepared. Then 77.6 g of bromine
A solution of (485 mmol) mixed with 240 ml of methylene chloride was added to the dropping funnel. The mixture was added dropwise over 68 minutes while stirring the mixture from the dropping funnel, and after completion of the addition, the mixture was further stirred for 1 hour to complete the reaction. Then, the ice water bath was removed, the temperature was raised to room temperature with stirring, and then the stirring was maintained for 1 hour to form triphenylphosphine oxide microcrystals. Then concentrate under reduced pressure,
Methylene chloride and hydrogen bromide were removed to obtain a sludge. Next, after 3,850 ml of hot n-hexane is added and dissolved, cooling crystallization is carried out, most of triphenylphosphine oxide which is white needle crystals is removed by filtration, and the filtrate is concentrated to obtain a syrupy residue. The The residue was purified by silica gel column chromatography (eluent n-hexane) to obtain colorless, clear liquid 4-ethoxybutyl bromide [yield 70.2 g (388 mmol) yield 80%].

Next, 10.9 g (456 mmol) of metallic magnesium and 76 ml of dry diethyl ether are placed in a nitrogen-exchanged flask equipped with a thermometer, stirrer, reflux condenser, dropping funnel and nitrogen insertion cock, and then iodine 0 is added. Add 1 g (0.38 mmol). The mixture was stirred until the reddish brown color disappeared. Then 6.9 g (38 mmol) of 4-ethoxybutyl bromide obtained above
Was added and stirred to reflux. If reflux occurs, 4-
61.9 g (342 mmol) of ethoxybutyl bromide
And 190 ml of dry diethyl ether were added to the dropping funnel and added dropwise to maintain reflux, and after completion of the addition, the mixture was refluxed for 1 hour to complete the reaction. Then, the reaction solution is taken out from the flask with a syringe, and the remaining unreacted metal magnesium solid is washed with 114 ml of dry ether, and the washing solution is returned to the reaction solution, and diethyl ether of 4-ethoxybutylmagnesium bromide at a concentration of 0.8 mol / liter. Solution 3
A Grignard reagent was obtained which was 80 ml [4-ethoxybutylmagnesium bromide [yield 62.3 g (304 mmol) yield 80%].

Reference Example 3 [(S) -1-hydroxy-2,
Production of 2,2-Trifluoroethyl-4-Ethoxybutyl Ketone] A four-neck round bottom flask equipped with a thermometer, a stirrer, a reflux condenser and a dropping funnel was subjected to 0.8 mol / 371 ml of a Grignard reagent of 1 [60.9 g (297 mmol) of 4-ethoxybutyl magnesium bromide, remaining diethyl ether] was added, and it was immersed in an ice water bath and adjusted to 0 ° C. A solution obtained by adding 200 ml of diethyl ether to 26.6 g (135 mmol) of (S) -N- (2-hydroxy-3,3,3-trifluoropropionyl) pyrrolidine obtained in Reference Example 1 was added to a dropping funnel and dissolved. The reaction solution was added dropwise with stirring over 60 minutes, and after completion of the dropwise addition, the reaction was continuously completed by continuing stirring for 2 hours to obtain a reaction product solution. The ice water bath was then removed and allowed to warm to room temperature while stirring. Next, 160 ml of 3 N hydrochloric acid was put into the dropping funnel and 2
It dripped over 3 minutes. After completion of the dropwise addition of 3 N hydrochloric acid, the hydrolysis reaction was completed by maintaining the stirring for 20 minutes.

After completion of the hydrolysis reaction, 20 % Sodium bicarbonate
After adjusting to pH 8 with aqueous lithium solution, extract with ether,
The extract is washed with water and then anhydrous magnesium sulfate is added
After removing the water, the solvent was removed by
Obtained a residue. The residue is subjected to silica gel column chromatography
[Eluent n-hexane / isopropyl alcohol
= 9/1 (volume ratio)] to form a colorless and transparent liquid
Product [yield 18.5 g (81 mmol) yield 60%] is obtained
The Of this product¹H NMR spectrum,¹⁹F NMR
Spectrum, 1R absorption spectrum and MS spectrum
The measured results are as follows, 1-hydroxy-2,
2,2-Trifluoroethyl-4-ethoxybutyl keto
Was confirmed. Note that from the identification example 1 described later
The product is (S) -1-hydroxy-2,2,2-trif
Be a fluoroethyl-4-ethoxybutyl ketone
confirmed.

¹ H NMR spectrum (CDCl ₃ ) 0.94 to 1.08 ppm (3 H), 1.18 to 1.4
8 ppm (6 H), 2.61 to 2.80 ppm (2
H), 3.20 to 3.35 ppm (2H), 3.46 to
3.78 ppm (1 H), 4.21 to 4.31 ppm
(1H) ¹⁹ F NMR spectrum (from ext. CF ₃ C
OOH)-4.66 ppm 1R absorption spectrum 1,120 cm ^-1 (COC), 1,670 cm ^-1 (C
O), 3,280 cm ^-1 (OH) MS spectrum m / z 228 (M ⁺ ) Also, the ¹ H NMR spectrum is shown in FIG.

Identification Example 1 [Identification that the product is (S) -1-hydroxy-2,2,2-trifluoroethyl-4-ethoxybutyl ketone] (S) -N- (2-) In place of hydroxy-3,3,3-trifluoropropionyl) pyrrolidine, N- (2-hydroxy-3,3,3-trifluoropropionyl) pyrrolidine is used, and it is the above 1/10 scale of the above-mentioned experiment. In the same manner as above, and the colorless and transparent liquid product-1 [yield 1.85 g (8.1 mmol) yield 60%]
I got The results of measuring various spectra of this product-1 were the same as above, and were 1-hydroxy-2,2,2-trifluoroethyl-4-ethoxybutyl ketone.

This product-1 was subjected to gas chromatography (hereinafter referred to as
It is called optically active gas chromatography. ). Column: Trade name CHIRALDEX, B-TA (ASTEC) ID 0.25 mm, length 10 m, silica capillary column Column temperature: 100 ° C × 10 minutes After holding, heat up to 200 ° C at a heating rate of 4 ° C / min. Carrier gas: Helium, gas flow rate 70 Nl / min, split ratio 100/1 Detection: FID The chart of optically active gas chromatography is as shown in Fig. 2. From the analysis result of Fig. 2, two optically active peaks are obtained. The peak retention time and area ratio of these peaks are determined as follows: First peak: retention time 34.67 minutes, area ratio 1 (S) body ☆ 1 Second peak: retention time 37.67 minutes, area ratio 1 (R) body ☆ 1 (* 1 confirmed in this identification example) Therefore, product-1 is 1-hydroxy-2,2,2
Enantiomeric mixture of trifluoroethyl-4-ethoxybutyl ketone.

Next, the product obtained above was subjected to optically active gas chromatography under the same conditions as above. The chart of optically active gas chromatography is as shown in FIG. 3. From FIG. 3, one optically active peak was obtained, and its retention time was 34.67 minutes. The product is obtained by replacing the N-pyrrolidinyl group of the starting material compound (S) -N- (2-hydroxy-3,3,3-trifluoropropionyl) pyrrolidine with 4-ethoxybutyl group in a Grignard reagent. Is obtained. Therefore, it was confirmed that it is (S) configuration because it is irrelevant to the configuration of the asymmetric carbon atom at the 2 position and optical inversion does not occur before and after the reaction. Therefore, the retention time of 34.67 minutes of optically active gas chromatography of the product was found to be (S) isomer, and the product was (S) -1-hydroxy-2,
It was confirmed to be 2,2-trifluoroethyl-4-ethoxybutyl ketone. The retention time of the second peak of optically active gas chromatography of product-1 37.
It turned out that 67 minutes were (R) form.

Reference Example 4 [(S) -2- (4-benzyloxybenzoyloxy) -7-ethoxy-1,1,1-
Preparation of trifluoroheptanone-3] A four-necked round-bottomed flask equipped with a thermometer, a stirrer, a reflux condenser and a dropping funnel was washed with n-hexane, purified, and dried, 1.99 g (83 mmol) of sodium hydride. ) And diethyl ether (23 ml) were inserted into an ice water bath and a suspension at 0 ° C was prepared while stirring. Next, (S) -1-hydroxy- obtained in Reference Example 3 was added to the dropping funnel.
Add 17.0 g (75 mmol) of 2,2,2-trifluoroethyl-4-ethoxybutyl ketone and 202 ml of diethyl ether to make a homogeneous solution and stir 1
It dripped over 7 minutes. After the addition was completed, the ice water bath was removed, and while stirring, the temperature was raised to 25 ° C., and the stirring was continued for 60 minutes to complete the reaction. Then, the above-mentioned flask was again inserted into an ice water bath and adjusted to 0 ° C. Separately into the dropping funnel, 22.2 g (90 mmol) of 4-benzyloxybenzoyl chloride and diethyl ether 108
The ml was charged and added dropwise over 33 minutes while stirring.
After the addition is complete, remove the ice water bath and while stirring, 25
The reaction was completed by raising the temperature to ° C. and then maintaining the stirring for 150 minutes.

After completion of the reaction, add 75 ml of 1 N hydrochloric acid,
After stirring for 60 minutes, the pH was adjusted to 8 with 5% aqueous sodium hydrogen carbonate solution. The extract is washed with water, and anhydrous magnesium sulfate is added to remove water, concentrated under reduced pressure, the solvent is distilled off, and the remaining pale yellow syrupy residue is subjected to silica gel column chromatography. 0.52 g of granular activated carbon in the solution purified by chromatography [eluent n-hexane / isopropyl alcohol = 96/4 (volume ratio)] [addition amount of granular activated carbon is (S) -1-hydroxy-2,2,2,2 3% by weight relative to the charge of trifluoroethyl-4-ethoxybutyl ketone. After stirring for 30 minutes, the granular activated carbon is removed by filtration, the filtrate is concentrated under reduced pressure, the eluent is distilled off, and a colorless transparent liquid product [yield 26.3 g (60 mmol) is obtained. 80%]. ¹ H NMR of this product
The results of measurement of the spectrum, ¹⁹ F NMR spectrum, 1R absorption spectrum and MS spectrum are as follows, and the product is 2- (4-benzyloxybenzoyloxy) -7-ethoxy-1,1,1-trifluorohepta It was confirmed to be non-3.

¹ H NMR spectrum (CDCl ₃ ) 1.07 ppm (3 H), 1.18 to 1.48 ppm
(6H), 2.92 to 3.04 ppm (2H), 3.2
4 to 3.35 ppm (2H), 4.17 to 4.27 pp
m (1 H), 4.49-4.67 ppm (2 H), 7.
25 ppm (2H), (6.75 to 7.00, 7.76
-7.95 ppm (4H, AB pattern) ¹⁹ F NMR spectrum (from ext. CF ₃ C
OOH) -5.5 ppm 1R absorption spectrum (neat) 1,110 cm ^-1 (COC), 1,660 cm ^-1 (C
O), 1,740 cm ^-1 (COO) MS spectrum m / z. 438 (M ⁺ ) Also, ¹ H NMR spectrum is shown in FIG.

Identification Example [The product obtained in Reference Example 4 is (S) -2- (4-benzyloxybenzoyloxy)
Identification as being -7-ethoxy-1,1,1-trifluoroheptanone-3] A four-necked round bottom flask equipped with a thermometer, a stirrer, a reflux condenser, and a dropping funnel, obtained as described above 2.19 g of product
(5 mmol), 25 ml of 3N hydrochloric acid and methanol 1
The reaction solution was immersed in a hot water bath at a temperature of 80 ° C., heated to a boiling temperature while stirring, and then refluxed for 6 hours to carry out a hydrolysis reaction. Then, after cooling to room temperature, extraction with ether is carried out, and the extract is washed with 20 ml of 20% aqueous sodium hydrogen carbonate solution and then with 200 ml of water, then anhydrous magnesium sulfate is added to remove water, and the solvent is distilled under reduced pressure. Removed to give a syrupy residue. The residue was subjected to silica gel column chromatography [eluent n
-Hydrogen / isopropyl alcohol = 90/10 (volume ratio)], colorless and transparent liquid product [yield 0.
91 g (4 mmol) yield 80%] was obtained.

When various spectra of the obtained product are measured, various spectral analysis of (S) -1-hydroxy-2,2,2-trifluoroethyl-4-ethoxybutyl ketone which is a starting compound of Reference Example 4 And when applied to optically active gas chromatography, the retention time is 3
4.67 minutes were confirmed to be in the (S) configuration, and the product was the same as the starting compound (S) -1-hydroxy-2,
It was found to be 2,2-trifluoroethyl-4-ethoxybutyl ketone. Therefore, an alkali metal hydride is reacted with a hydroxyl group bonded to the asymmetric carbon atom at position 1 of (S) -1-hydroxy-2,2,2-trifluoroethyl-4-ethoxybutyl ketone to give an alkali metal alcoholate. And then reacting with 4-benzyloxybenzoyl chloride does not change the absolute configuration,
It is confirmed that (S) configuration is obtained, and the product is (S) -2
It was confirmed to be-(4-benzyloxybenzoyloxy) -7-ethoxy-1,1,1-trifluoroheptanone-3.

Reference Example 5 [syn- (2S, 3R) -2-
(4-hydroxybenzoyloxy) -7-ethoxy-
3-methoxy-1,1,1-trifluoroheptane and anti- (2S, 3S) -2- (4-hydroxybenzoyloxy) -7-ethoxy-3-methoxy-1,
Production of 1,1-trifluoroheptane (raw material compound):
However, when a stable aqueous solution of sodium borohydride is used as a metal hydride] (first stage reaction) [syn isomer (2S, 3R) type / anti]
Production of a reaction product which is a diastereomeric mixture consisting of body (2S, 3S) type = 70/30 (area ratio)] Four-necked round-bottomed flask equipped with a thermometer, a stirrer, a reflux condenser and a dropping funnel (S) -2 obtained in Reference Example 4
-(4-benzyloxybenzoyloxy) -7-ethoxy-1,1,1-trifluoroheptanone-3, 1
0.95 g (25 mmol) and 40 m of diethyl ether
The solution was poured into a homogeneous solution while stirring, inserted into an ice water bath, and adjusted to 0.degree.

Next, a stabilized aqueous solution of sodium borohydride containing 0.27 g (7 mmol) of sodium borohydride, 28 g of a 5% aqueous solution of sodium hydroxide (1.4 g (35 mmol) of NaOH) and 7 ml of methanol in a dropping funnel Was added dropwise over 10 minutes while stirring. After the addition is complete, remove the ice water bath and while stirring,
The temperature was raised to room temperature, and then stirring was continued for 90 minutes to complete the reaction and obtain a reaction product. The resulting reaction product solution was obtained from the identification example 1 described below: syn form (2S, 3R) type / anti form (2S, 3S) type = 70/30 (area ratio)
It was confirmed that the mixture was a mixture of diastereomers.

Identification Example 1: The reaction product is a syn isomer (2
S, 3R) / anti body (2S, 3S) = 70/3
Identification of being a diastereomeric mixture consisting of 0 (area ratio)] In a three-necked round bottom flask equipped with a thermometer, a stirrer and a reflux condenser, the above-obtained 40% by weight reaction product solution [raw material Compound conversion 10 mmol containing reaction product solution], 50 ml of 3 N hydrochloric acid and methanol 20
0 ml was introduced, inserted into a hot water bath at a temperature of 80%, and while stirring, the temperature was raised to a boiling point, and then the mixture was heated to reflux for 7 hours to carry out a hydrolysis reaction.

After completion of the hydrolysis reaction, remove the hot water bath, cool to room temperature while stirring, extract with ether, extract 40 ml of 20% aqueous sodium hydrogen carbonate solution
After washing with 300 ml of water, anhydrous magnesium sulfate was added to remove water, and then the solvent was evaporated under reduced pressure to obtain a syrupy residue. The residue was purified by silica gel column chromatography [eluent n-hexane / isopropyl alcohol = 95/5 (volume ratio)] to give colorless transparent liquid product-1 [yield 1.84 g (8
ppm) yield 80%]. ¹ HN of this product- ¹
As a result of measuring an MR spectrum, ¹⁹ F NMR spectrum, 1R absorption spectrum and MS spectrum, the product
1 was found to be 7-ethoxy-1,1,1-trifluoroheptane-2,3-diol.

¹ H NMR spectrum (CDCl ₃ ) 0.86 to 1.00 ppm (3 H), 1.06 to 1.2
4 ppm (6 H), 2.69 to 2.80 ppm (2
H), 2.95 to 3.16 ppm (1 H), 3.20 to
3.35 ppm (2H), 3.52 to 3.66 ppm
(2H), 4.08 to 4.16 ppm (1H) ¹⁹ F NMR spectrum (from ext. CF ₃ C
OOH) 1st peak: -0.48 ppm, area ratio 70% [Syn
Body (2S, 3R) type ☆ 1] Second peak: -2.21 ppm, area ratio 30% [ant
i form (2S, 3S) type] 1] (☆ 1 confirmed in this identification example) 1R absorption spectrum (neat) 1,150 cm ^-1 (COC), 3,270 cm ^-1 (O
H) MS spectrum m / z. 230 (M ⁺ ) Also, the ¹ H NMR spectrum is shown in FIG.

Then, the product obtained above in a three-necked round bottom flask equipped with a thermometer, a stirrer and a reflux condenser,
Add 1.15 g (5 mmol), 5 ml of 2.2-dimethoxypropane and 0.1 mg of p-toluenesulfonic acid monohydrate, and insert in a hot water bath at a temperature of 90 ° C., while stirring,
The temperature is raised to boiling and reflux is continued for 5 hours to carry out acetal exchange reaction. After completion of the reaction, the reaction product is distilled at 82 ° C., and the fraction is concentrated to give a colorless and transparent liquid product-1.
I got ¹ H NMR spectrum of this product-2, ¹⁹ F
The results of measurement of NMR spectrum, 1R absorption spectrum and MS spectrum are as follows, and product-2 is 2,2-dimethyl-4- (4-ethoxybutyl) -5-
Trifluoromethyl-1,3-dioxolane (hereinafter referred to as
It is called a 1,3-dioxolane derivative. ) Was confirmed.

¹ H NMR spectrum (CDCl ₃ ) 1.00 to 1.05 ppm (3 H), 1.36 to 2.0
7 ppm (6 H), 1.58 ppm (CH ₃ ), 1.7
_{5ppm (CH 3), 1.82ppm (} CH 3), 1.9
0 ppm (CH ₃ ), 2.73 to 2.84 ppm (2
H), 2.95 to 3.04 ppm (2H), 3.55 to 5
3.80 ppm (2H) ¹⁹ F NMR spectrum (from ext. CF ₃ C
OOH) 1st peak: -0.46 ppm, area ratio 70% [tra
ns form 1,3-dioxolane derivative ☆ 2] Second peak: -3.66 ppm, area ratio 30% [cis
Body 1,3-Dioxolane Derivative ☆ 2] (Confirmed by ☆ 2 Identification Example) 1 R Absorption Spectrum (neat) 1,140 cm ⁻¹ (OH), MS Spectrum m / z. 270 (M ⁺ ) Also, the ¹ H NMR spectrum is shown in FIG.

Further, the product-2 obtained above is 1, 3
The position and area ratio of the methyl group in the ¹ H NMR spectrum of the dioxolane derivative are as shown in Table 1. Table 1
Therefore, the position of the methyl group which is 70% of area ratio
-2, 2-Dimethyl-4- (4-ethoxybutyl) -5
Trifluoromethyl-1,3-dioxolane (hereinafter referred to as
It is called a trans 1,3-dioxolane derivative. The position of the methyl group which is 30% in area ratio is
2,2-Dimethyl-4- (4-ethoxybutyl) -5-
Trifluoromethyl-1,3-dioxolane (hereinafter referred to as c)
The compound is referred to as a 1,3-dioxolane derivative. It turned out to be). Thus, product-2 is trans-
2,2-Dimethyl-4- (4-ethoxybutyl) -5-
Trifluoromethyl-1,3-dioxolane and ci
It consists of s-2,2-2 dimethyl 4- (4-ethoxy butyl) -5- trifluoromethyl 1- 3-dioxolane, and the formation ratio trans body / cis body = 70
It was confirmed that the mixture was a / 30 (area ratio) diastereomer mixture.

[0045]

[Table 1]

[0046] Further, ¹ HNMR spectrum methyl group of the product -2 (1.75ppm, 1.82ppm) an area ratio of 70% of trans-isomer 1,3-dioxolane derivative of the ¹⁹ FNMR spectrum of the product -2 By matching the area ratio of the first peak (-0.46 ppm),
The first peak is a trans 1,3-dioxolane derivative, which is a methyl group (1.58p) in the ¹ H NMR spectrum.
¹⁹ F NMR of cis 1,3-dioxolane derivative and product-2 having an area ratio of 30% of pm, 1.90 ppm)
As the area ratio of the second peak (-3.66 ppm) of the spectrum is matched, the second peak is a cis 1,3-form.
It was confirmed to be a dioxolane derivative.

Also, the reaction product obtained in the first step reaction described above is (S) -2- (4-benzyloxybenzoyloxy) -7-ethoxy-1,1,1-trifluoroheptanone-3. The asymmetric carbon atom at position 2 is not related to the reduction reaction and was confirmed to be of the (2S) configuration, since it is obtained by reducing the carbonyl carbon of the compound with a metal hydride. Also, 7-ethoxy-1,1,1-trifluoroheptane-2,3-hydrolyzed of the obtained reaction product
The asymmetric carbon atom at position 2 of the diol was confirmed to be the (2S) configuration by the fact that the absolute configuration does not change upon hydrolysis.

Accordingly, the first peak (-0.48) of the ¹⁹ F NMR spectrum of the product-1 which has the same area ratio as the trans-form 1,3-dioxolane derivative of the product-2
ppm) is syn- (2S, 3R) -7-ethoxy-
¹⁹ F NMR of product 1, which is 1,1,1-trifluoroheptane-2,3-diol, while the area ratio matches the cis 1,3-dioxolane derivative of product-2
The second peak of the spectrum (-2.21 ppm) is ant
i- (2S, 3S) -7-Ethoxy-1,1,1-trifluoroheptane-2,3-diol is found and the product-1 is syn- (2S, 3R) -7-ethoxy -1,1,1-trifluoroheptane-2,3-diol and anti- (2S, 3S) -7-ethoxy-
It consists of 1,1,1-trifluoroheptane-2,3-diol, and its formation ratio syn form (2S, 3R) type / a
It was confirmed that the nti isomer (2S, 3S) form = 70/30 (area ratio) was a diastereomer mixture. Therefore, the reaction product obtained in the first step reaction is a syn compound (2
S, 3R) / anti body (2S, 3S) = 70/3
It could be confirmed that this was a mixture of diastereomers consisting of 0 (area ratio).

(Second Stage Reaction) (Production of O-Methylated Derivative) In a round bottom flask equipped with a thermometer, a stirrer, a reflux condenser and a dropping funnel, the remaining 60% obtained in the first stage reaction Add the reaction product solution [(S) -2- (4-benzyloxybenzoyloxy) -1,1,1-trifluoro-7-ethoxyheptanone-a solution containing 15 millimoles converted] in an ice water bath And adjusted to 0.degree. C. with stirring. Then add methyl iodide 2.27g to the dropping funnel
Put (16 mmol) and 20 ml of diethyl ether,
It was added dropwise over 11 minutes while stirring. After completion of dripping
Remove the ice water bath and warm up to room temperature while stirring,
Subsequently, stirring was maintained at room temperature for 2 hours to complete the reaction.

After completion of the reaction, the reaction solution is neutralized by the addition of a 5% aqueous solution of sodium hydrogen carbonate, and the solvent is distilled off under reduced pressure. A saturated aqueous solution of sodium thiosulfate solution is then added, followed by extraction with ether and extraction with anhydrous magnesium sulfate. The reaction mixture was concentrated to dryness under reduced pressure to give a syrupy residue. The residue is subjected to silica gel column chromatography [eluent n-hexane / isopropyl alcohol = 95/5 (volume ratio)]
To give a colorless, clear liquid O-methylated derivative [yield 5.79 g (12.75 mmol) yield 85%]. As a result of measuring the ¹⁹ F NMR spectrum of the obtained O-methylated derivative, two peaks are recognized, and the position and area ratio of each peak are shown as follows: ¹⁹ F NMR spectrum (from ext. CF ₃ C
OOH) 1st peak: -2.20 ppm, area ratio 70%, [Sy
n-form (2S, 3R) type ☆ 3] Second peak: −3.90 ppm, area ratio 30%, [an
ti form (2S, 3S) type 3 3] (☆ 3, confirmed in identification example 2 described later) Therefore, according to the result of ¹⁹ F NMR spectrum and identification example 2 described later, the O-methylated derivative is a syn isomer (2S,
3R) type / anti body (2S, 3S) type = 70/30
It was confirmed to be a mixture of diastereomers consisting of (area ratio).

(Third Stage Reaction) A sealed 4-neck round bottom flask equipped with a thermometer, stirrer, dropping funnel, hydrogen gas charge pipe and polyethylene resin balloon was obtained by the above-mentioned second stage reaction. 3.86 g (8.5 mmol) of O-methylated derivative and 58 ml of methanol are charged, and 10% palladium / carbon catalyst 0.0 is added to the dropping funnel while stirring at room temperature.
8 g was added and slowly dropped to prepare a uniformly dispersed suspension. Then pressure 1.1 with stirring at room temperature
The reaction system was sealed with hydrogen gas of about kg / cm ² and reduction reaction was performed. In the reduction reaction, the suspension was stirred, and supplied for 4 hours until absorption of hydrogen gas ceased to complete the reaction.

After completion of the reduction reaction, the resulting reaction suspension is filtered to remove the palladium / carbon catalyst, and the filtrate is concentrated under reduced pressure to distill off methanol, and then by-product toluene is vacuum-pumped. Removal gave a syrupy residue. The residue was subjected to silica gel column chromatography [eluent n-hexane / isopropyl alcohol = 96
/ 4 (volume ratio)], the eluent was distilled off under reduced pressure, and diastereomer mixture-1 as a colorless and transparent liquid product
[A yield of 3.03 g (8.33 mmol) of 98% yield] was obtained. ¹ H NMR spectrum of this product, ¹⁹ F NMR
The results of measuring the spectrum, 1R absorption spectrum, and MS spectrum are as follows, and the product is 2- (4)
-Hydroxybenzoyloxy) -7-ethoxy-3-
It was confirmed to be methoxy-1,1,1-trifluoroheptane.

[0053]¹H NMR spectrum (CDCl₃) 0.87 to 0.96 ppm (3H), 1.09 to 1.5
3 ppm (6 H), 2.60 to 2.72 ppm (2
H ), 2.75 ppm (3H), 2.87 to 3.00 p
pm (1 H), 3.27 to 3.42 ppm (2 H),
4.18 to 4.35 ppm (1H), 5.41 ppm
(1H), 6.69 to 7.98 ppm (4H, AB puta
ー)¹⁹ F NMR spectrum (from ext. CF₃C
OOH) 1st peak: -1.86 ppm, area ratio 70% [Syn
Body (2S, 3R) type ☆ 4] Second peak: -2.33 ppm, area ratio 30% [ant
i-form (2S, 3S) type ☆ 4] (☆ 4, confirmed in Identification Example 2 described later) 1R absorption spectrum 1,110 cm^-1(COC), 1,740 cm^-1(CO
O), 3,300 cm^-1(OH), MS spectrum m / z. 364 (M⁺) Also,¹The HNMR spectrum is shown in FIG.

The product obtained is, according to the identification example 2 described later, s
yn- (2S, 3R) -2- (4-hydroxybenzoyloxy) -7-ethoxy-3-methoxy-1,1,1
A diastereomeric mixture consisting of trifluoroheptane and anti-2- (4-hydroxybenzoyloxy) -7-ethoxy-3-methoxy-1,1,1-trifluoroheptane, and the formation ratio syn isomer (2
S, 3R) / anti body (2S, 3S) = 70/3
It was confirmed that it is diastereomer mixture-1 which is 0 (area ratio).

Identification Example 2: The O-methylated derivative obtained by the second step reaction is a dia consisting of syn form (2S, 3R) type / anti form (2S, 3S) type = 70/30 (area ratio) It is a stereomeric mixture, and the diastereomeric mixture-1 obtained in the third step reaction is syn- (2S, 3)
R) -2- (4-hydroxybenzoyloxy) -7-
It is composed of ethoxy-3-methoxy-1,1,1-trifluoroheptane and anti- (2S, 3S) -7-ethoxy-3-methoxy-1,1,1-trifluoroheptane, and the formation ratio syn isomer ( 2S, 3R) type / an
Identification of the diastereomer mixture-1 of ti form (2S, 3S) = 70/30 (area ratio)] In a four-neck round bottom flask equipped with a thermometer, a stirrer, a reflux condenser, and a funnel First, 1.82 g (4 mmol) of the O-methylated derivative obtained in the second step reaction of Example 1, 20 ml of 3N hydrochloric acid and 80 ml of methanol were added, and the temperature was raised to 80 ° C. with stirring for 6 hours. Reflux to obtain a hydrolysis reaction. Then
After cooling to room temperature, extract with ether and extract 20%
After washing with an aqueous solution of sodium hydrogen carbonate and then with water, anhydrous magnesium sulfate is added to remove water, and then the solvent is distilled off under reduced pressure to obtain a colorless and transparent liquid product [yield 0.78 g (3. 2 mmol) yield 80%] was obtained.

Of this product¹H NMR spectrum,¹⁹F
NMR spectrum, 1R absorption spectrum, and MS spectrum
The results of measuring the spectra are as follows, and the product is 2
-Hydroxy-7-ethoxy-3-methoxy-1,1,
It was 1-trifluoroheptane.¹ H NMR spectrum (CDCl₃) 0.81 to 1.00 ppm (3H), 1.04 to 1.3
0 ppm (6 H), 2.48 to 2.64 ppm (3
H ), 2.69 ppm (3H), 2.84 to 3.00 p
pm (1 H), 3.12 to 3.26 ppm (2 H),
3.77 to 3.90 ppm (1 H), 4.02 to 4.1
4 ppm (1 H)¹⁹ F NMR spectrum (from ext. CF₃C
OOH) 1st peak: -2.12 ppm, area ratio 70% [Syn
Body (2S, 3R) type ☆ 5] Second peak: -4.14 ppm, area ratio 30% [ant
i form (2S, 3S) type ☆ 5] (☆ 5, confirmed by this identification example) 1R absorption spectrum (neat) 1,120 cm^-1(COC), 1,670 cm^-1(O
H), MS spectrum m / z 244 (M⁺) Also,¹The HNMR spectrum is shown in FIG.

Then, the above-mentioned product was subjected to gas chromatography (hereinafter referred to as optically active gas chromatography) having a column for separating optical isomers under the following conditions. Column: trade name Cyclodex β 236 M (made by Chrompack): size: inner diameter 0.25 mm, length 25 m: silica capillary column column temperature: 100 ° C. for 10 minutes and then raised to 200 ° C. at a heating rate of 4 ° C./min. Temperature Carrier gas: Helium, gas flow rate 60 NL / min, split ratio 100/1 Detection: FID

The chart of optically active gas chromatography is shown in FIG. From the analysis results of the chart in FIG. 9, two optically active peaks are observed, and the retention time and the area ratio of each peak are as follows. First peak: retention time 14.55 minutes, area ratio 70%,
[Syn form (2S, 3R) type ☆ 6] Second peak: retention time 15.27 minutes, area ratio 30%,
[Anti body (2S, 3S) type ☆ 6] (confirmed with this example ☆ 6 identification)

The syn form (2S, 3) obtained in the first step reaction
Alcoholates and methyl iodides of metal compounds bound to the asymmetric carbon atom at position 3 of the reaction product which is a diastereomeric mixture consisting of R) type / anti form (2S, 3S) type = 70/30 (area ratio) The product obtained by acid hydrolysis of the O-methylated derivative obtained by reacting with a compound gives two optically active peaks, and the first peak / second peak = 70/30 (area That the absolute configuration of the asymmetric carbon atom at the 2-position and the 3-position does not change between the reaction product and the product because the ratio (A) corresponds to the area ratio of the reaction product obtained in the first step reaction Was confirmed.

Therefore, the first peak (retention time 1) which is 70% of the area ratio of product optically active gas chromatography
4.55 minutes) is syn- (2S, 3R) -2-hydroxy-7-ethoxy-3-methoxy-1,1,1-trifluoroheptane, while the area ratio of optically active gas chromatography is 30% Second peak (retention time 1
5.27 min) was found to be anti- (2S, 3S) -2-hydroxy-7-ethoxy-3-methoxyheptane, syn- (2S, 3R) -2-hydroxy-
First peak of the ¹⁹ F NMR spectrum of the product having the same area ratio as 7-ethoxy-3-methoxyheptane (-2.
12 ppm) is syn- (2S, 3R) -2-hydroxy-7-ethoxy-3-methoxy-1,1,1-trifluoroheptane, while anti- (2S, 3
S) -2-hydroxy-7-ethoxy-3-methoxy-
The second peak (-4.1) of the ¹⁹ F NMR spectrum of the product having the same area ratio as 1,1,1-trifluoroheptane
4 ppm) was confirmed to be anti- (2S, 3S) -2-hydroxy-7-ethoxy-3-methoxy-1,1,1-trifluoroheptane.

Accordingly, the product obtained by hydrolyzing the O-methyl derivative and the 2-position and 3 each of the O-methylated derivative
As the absolute configuration of the asymmetric carbon atom at the position does not change,
70% of area ratio of ¹⁹ F NMR spectrum of methylated derivative
Is the first peak (-2.20 ppm) is syn compound (2
S, 3R) type, with an area ratio 3 of ¹⁹ F NMR spectrum
The second peak (-3.90 ppm) at 0% is anti
Body (2S, 3S) type was found, and the O-methylated derivative was syn (2S, 3R) type / anti (2
It was confirmed that the mixture was a mixture of diastereomers consisting of S, 3S) type = 70/30 (area ratio).

Then, the diastereomer mixture-1 obtained in the third step reaction was subjected to optically active liquid chromatography under the following conditions. Optical isomer separation column: [trade name: HPLC for separating amylose optical isomers Column: manufactured by Daicel Chemical Industries, Ltd.] Separation agent: amylose tris [(S) -1-phenylethyl carbamate] is coated with silica gel What (Great CHIRALPAKAS) Size: 4.6 mmφ × 250 mm H Eluent: n-hexane / isopropyl alcohol = 96/4 (volume ratio) Flow rate: 0.5 ml / min. Detection: UV absorption at a wavelength of 254 mm was used as a UV detector. Sample: 0.1 mg

The chart of the optically active liquid chromatography is as shown in FIG. 10, and from the analysis result of FIG.
Two optically active peaks were obtained, and their retention time and area ratio were as follows. First peak [syn- (2S, 3R) -2- (4-hydroxybenzoyloxy) -7-ethoxy-3-methoxy-1,1,1-trifluoroheptane ☆ 7] retention time 10.11 minutes area ratio 70% second peak [anti- (2S, 3S) -2- (4-hydroxybenzoyloxy) -7-ethoxy-3-methoxy-1,1,1-trifluoroheptane ☆ 7] retention time 11.46 minutes Area ratio 30% (Checked from this example of ☆ 7 identification)

Incidentally, according to the above-mentioned identification example 2, syn body (2
S, 3R) / anti body (2S, 3S) = 70/3
O which is a mixture of diastereomers consisting of 0 (area ratio)
Diastereomeric mixtures by reducing methylated derivatives with hydrogen gas in the presence of a palladium / carbon catalyst
In the reaction from which 1 is obtained, it is irrelevant to the configuration of the asymmetric carbon atom at the 2- and 3-positions. Therefore, the first peak (retention time: 10.11 minutes) of optically active liquid chromatography of diastereomeric mixture-1 corresponding to the area ratio of the syn isomer (2S, 3R) of the O-methylated derivative is syn
-(2S, 3R) -2- (4-hydroxybenzoyloxy) -7-ethoxy-3-methoxy-1,1,1-trifluoroheptane, while the anti form of O-methylated derivative (2S, 3S The second peak (retention time 11.46 minutes) of optically active liquid chromatography of diastereomer mixture 1 in agreement with the area ratio of type) is the anti-
It was found to be (2S, 3S) -2- (4-hydroxybenzoyloxy) -7-ethoxy-3-methoxy-1,1,1-trifluoroheptane.

Thus, ^{19 of} diastereomer mixture-1
The first peak (-1.86 ppm), which has an area ratio of 70% in the FNMR spectrum, is syn- (2S, 3R) -2-
(4-hydroxybenzoyloxy) -7-ethoxy-
The second peak (−2.33 p) which is 3-methoxy-1,1,1-trifluoroheptane and has an area ratio of 30%
pm) was confirmed to be anti- (2S, 3S) -2- (4-hydroxybenzoyloxy) -7-ethoxy-3-methoxy-1,1,1-trifluoroheptane; 1 is syn- (2S,
3R) -2- (4-hydroxybenzoyloxy) -7
-Ethoxy-3-methoxy-1,1,1-trifluoroheptane and anti-2- (4-hydroxybenzoyloxy) -7-ethoxy-3-methoxy-1,1,-
It consists of 1-trifluoroheptane, and its production ratio sy
n-body (2S, 3R) type / anti body (2S, 3S) type =
It could be confirmed that the mixture was a 70/30 (area ratio) diastereomer mixture.

(Fourth stage reaction) [syn- (2S, 3R)
-2- (4-hydroxybenzoyloxy) -7-ethoxy-3-methoxy-1,1,1-trifluoroheptane (raw material compound) and anti- (2S, 3S) -2
Preparation of-(4-hydroxybenzoyloxy) -7-ethoxy-3-methoxy-1,1,1-trifluoroheptane] Diastereomer mixture obtained in the third step reaction 1, 2
The first peak and the second peak are separated respectively using 00 g (5.5 mmol) of silica gel column chromatography under the following conditions, the eluent is distilled off under reduced pressure, and both are colorless and transparent liquid Of the first fraction [acquisition amount 1.26 g (3.47 mmol) acquisition rate 63
%] And the second fraction [acquisition amount 0.54 g (1.
48 mmol) yield 27%] were obtained respectively.

¹ H NMR spectra of these products,
The 1 R absorption spectrum, MS spectrum is consistent with diastereomer mixture 1, and each product is 2- (4-hydroxybenzoyloxy) -7-ethoxy-3-methoxy-
It was 1,1,1-trifluoroheptane. Also, ¹⁹
The FNMR spectrum is as follows, and one peak was observed. Furthermore, optically active liquid chromatography was performed under the same conditions as in Identification Example 2 of the third step reaction. Each chart of the above-mentioned optically active liquid chromatography is shown in FIG.
As shown in FIG. 1 and FIG. 12, one optically active peak is obtained respectively from the analysis results of FIG. 11 and FIG. 12, and the retention time is as follows. The first fraction, which is the product, is syn -(2S, 3R) -2- (4-hydroxybenzoyloxy) -7-ethoxy-3-methoxy-1,1,1-trifluoroheptane (raw material compound), the second fraction is anti- (2S, 3S)-
It could be confirmed that this was 2- (4-hydroxybenzoyloxy) -7-ethoxy-3-methoxy-1,1,1-trifluoroheptane.

Preparative silica gel column chromatography [trade name: Inert Siel PREP-ODS fraction, guard column 2-point set No. 5020-35112, GL Science Co., Ltd.] Filler: one having an octadecyl group chemically bonded to 10 μ silica gel having a purity of 99.9% Size: 10 mmφ × 250 mm H Eluent: n-hexane / isopropyl alcohol = 96
/ 4 (volume ratio) Flow rate: 2 ml / min Detection: UV detector, wavelength 254 nm Sample supply amount: 1 g

The first fraction [syn-(2S, 3
R) -2- (4-hydroxybenzoyloxy) -7-
Ethoxy-3-methoxy-1,1,1-trifluoroheptane] Retention time 10.11 minutes Yield 1.95 g (5.36 mmol) yield 63% ¹⁹ F NMR spectrum (from ext. CF ₃ C
OOH) -1.86 ppm Optically active liquid chromatography: retention time 10.11
Minute second flankion [anti-(2S, 3S) -2-
(4-hydroxybenzoyloxy) -7-ethoxy-
3-methoxy-1,1,1-trifluoroheptane] retention time 11.46 minutes yield 0.83 g (2.30 mmol) yield 27% ¹⁹ F NMR spectrum (from ext. CF ₃ C
OOH) -2.33 ppm Optically active liquid chromatography: retention time 11.46
Minutes

Reference Example 6 [syn- (2S, 3R) -2-
(4-hydroxybenzoyloxy) -7-ethoxy-
3-methoxy-1,1,1-trifluoroheptane and anti- (2S, 3S) -2- (4-hydroxybenzoyloxy) -7-ethoxy-3-methoxy-1,
Production of 1,1-trifluoroheptane, provided that diisobutylaluminum hydride is used as metal hydride]

(First-step reaction) [syn form (2S, 3R)
Production of a reaction product which is a mixture of diastereomers consisting of type / anti form (2S, 3S) type = 40/60 (area ratio)] Four-neck, equipped with a thermometer, a stirrer, a reflux condenser and a dropping funnel (S) -2 obtained in Reference Example 4 in a round bottom flask
-(4-benzyloxybenzoyloxy) -7-ethoxy-1,1,1-trifluoroheptanone-3, 1
23 ml was added to 0.95 g (25 mmol), made into a homogeneous solution with stirring, inserted into an ice water bath, and adjusted to 0 ° C. Then, 3.91 g (27.5 mmol) of diisobutylaluminum hydride and 23 ml of diethyl ether were charged into the dropping funnel and added dropwise over 10 minutes while stirring. After the addition is completed, the ice water bath is removed, and while stirring, the temperature is raised to room temperature, and the stirring is continued for 90 minutes.
The reaction was completed to obtain a reaction product solution. The obtained reaction product is syn form (2S, 3R) according to the identification example 3 described later.
It was confirmed that the mixture was a mixture of diastereomers consisting of type / anti form (2S, 3S) type = 40/60 (area ratio).

Identification Example 3: The reaction product is a syn isomer (2
S, 3R) / anti body (2S, 3S) = 40/6
Identification of being a diastereomeric mixture consisting of 0 (area ratio)] 20% by weight reaction product solution (raw material compound obtained above in a three-neck round bottom flask equipped with a thermometer, a stirrer and a reflux condenser Reaction product solution containing 5 mmol), 25 ml of 3N hydrochloric acid and 100 m of methanol
The reaction mixture was introduced into a warm water bath at a temperature of 80.degree. C., and while stirring, the temperature was raised to a boil, followed by heating to reflux for 7 hours to carry out a hydrolysis reaction. After the hydrolysis reaction is completed, the hot water bath is removed, and after cooling to room temperature while stirring,
After extraction with ether, the extract was washed with 20 ml of 20% aqueous sodium hydrogen carbonate solution and then with 200 ml of water, anhydrous magnesium sulfate was added to remove water, and then the solvent was distilled off under reduced pressure to give a syrupy residue. I got The residue was subjected to silica gel column chromatography [eluent n
Purification with -hexane / isopropyl alcohol = 95/5 (volume ratio) to obtain a colorless and transparent liquid product-3 [yield 0.9 g (3.92 ppm) 78.4%].

¹ H NMR spectrum of this product-3,
^The results of measurement of ¹⁹ F NMR spectrum and 1 R absorption spectrum are in agreement with those of Identification Example 1 of Reference Example 5, and 7-ethoxy-
It was confirmed to be 1,1,1-trifluoroheptane-2,3-diol. Moreover, based on the result of the identification example 1 of the reference example 5, as a result of measuring a ¹⁹ F NMR spectrum, 2
From the position and area ratio of each peak, the product-3 is syn- (2S, 3R) -7-ethoxy-1,1,1-trifluoroheptane-2,3-diol and anti -(2S, 3S) -7-ethoxy-
It consists of 1,1,1-trifluoroheptane-2,3-diol, and its formation ratio syn form (2S, 3R) type / a
It turned out that it is a diastereomer mixture which consists of nti body (2S, 3S) type = 40/60 (area ratio). ¹⁹ F NMR spectrum (from ext. CF ₃ C
OOH) First peak: -0.48 ppm, area ratio 40 syn body (2S, 3R) type Second peak: -2.21 ppm, area ratio 60 anti
Body (2S, 3S) type Therefore, the reaction product syn body (2S, 3R) type / anti body (2S, 3S) type = 40 obtained in the first step reaction
It could be confirmed that this was a mixture of diastereomers consisting of / 60 (area ratio).

Second Stage Reaction (O-Methylated Derivative) The remaining 80% of the reaction product obtained in the first stage reaction is produced in a round bottom flask equipped with a thermometer, a stirrer, a reflux condenser and a dropping funnel. Solution [(S) -2- (4-benzyloxybenzoyloxy) -1,1,1-trifluoro-7-ethoxyheptanone-a solution containing 20 millimoles of 3-equivalent] is added and inserted into an ice water bath The mixture was adjusted to 0.degree. C. while stirring. Then add methyl iodide 3.12g to the dropping funnel
Put (22 mmol) and 28 ml of diethyl ether,
It was added dropwise over 13 minutes while stirring. After completion of dripping
The ice water bath was removed, the temperature was raised to room temperature, and stirring was continued at room temperature for 2 hours to complete the reaction.

After completion of the reaction, the reaction solution is neutralized by the addition of a 5% aqueous solution of sodium hydrogen carbonate, and the solvent is distilled off under reduced pressure. A saturated aqueous solution of sodium thiosulfate solution is then added, followed by extraction with ether and extraction with anhydrous magnesium sulfate. The reaction mixture was concentrated to dryness under reduced pressure to give a syrupy residue. The residue is subjected to silica gel column chromatography [eluent n-hexane / isopropyl alcohol = 95/5 (volume ratio)]
To give a colorless, clear liquid O-methylated derivative [yield 7.54 g (16.6 mmol) 83%].
As a result of measuring a ¹⁹ F NMR spectrum of the obtained O-methylated derivative, two peaks are recognized, and the position and area ratio of each peak are shown as follows. ¹⁹ F NMR spectrum (from ext. CF ₃ C
OOH) 1st peak: -2.20 ppm, area ratio 40% [syn
Body (2S, 3R) type ☆ 7] Second peak:-3.90 ppm, area ratio 60% [ant
i form (2S, 3S) type ☆ 7] (☆ 7, confirmed in the identification example 4 described later)

(Third Stage Reaction) A sealed 4-neck round bottom flask equipped with a thermometer, a stirrer, a dropping funnel, a hydrogen gas charge pipe and a polyethylene resin balloon was obtained by the above-mentioned second stage reaction. Add 4.99 g (11 mmol) of O-methylated derivative and 75 ml of methanol, and while stirring at room temperature, add 10% palladium / carbon catalyst to the dropping funnel.
g was added and slowly dropped to prepare a uniformly dispersed suspension. Then, while stirring at room temperature, the pressure 1.1 k
The reaction system was sealed with hydrogen gas of about g / cm ² and reduction reaction was performed. In the reduction reaction, the suspension was stirred, and supplied for 4 to 5 hours until absorption of hydrogen gas ceased to complete the reaction. After completion of the reduction reaction, the resulting reaction suspension is filtered to remove the palladium / carbon catalyst, and the filtrate is concentrated under reduced pressure to distill off methanol, and then by-product toluene is removed by a vacuum pump. A syrupy residue was obtained.
The residue was subjected to silica gel column chromatography [eluent n-hexane / isopropyl alcohol = 96/4
(Volume ratio)], and the eluent was distilled off under reduced pressure to obtain a colorless and transparent liquid product diastereomer mixture-2 [yield 3.92 g (10.78 mmol) yield 98%] The

¹ H NMR spectrum of this product, 1 R
The results of measuring the absorption spectrum and MS spectrum are the same as in the third step reaction of Reference Example 5, and the product is 2-
It was confirmed to be (4'-hydroxybenzoyloxy) -7-ethoxy-3-methoxy-1,1,1-trifluoroheptane. As a result of measuring the ¹⁹ F NMR spectrum of the obtained product, two peaks are observed, and the position and area ratio of each peak are shown as follows. ¹⁹ F NMR spectrum (from ext. CF ₃ C
OOH) 1st peak: -1.86 ppm, area ratio 40% [Syn
Body (2S, 3R) type ☆ 8] Second peak: -2.33 ppm, area ratio 60% [ant
i body (2S, 3S) type ☆ 8] (☆ 8, confirmed in the identification example 4 described later)

The product obtained is identified according to the identification example 4 described below.
yn- (2S, 3R) -2- (4-hydroxybenzoyloxy) -7-ethoxy-3-methoxy-1,1,1
-Trifluoroheptane and anti-(2S, 3
S) -2- (4-hydroxybenzoyloxy) -7-
It is a mixture of diastereomers consisting of ethoxy-3-methoxy-1,1,1-trifluoroheptane, and its formation ratio syn form (2S, 3R) type / anti form (2S,
It was confirmed that it is diastereomer mixture 2 which is 3S) type = 40/60 (area ratio).

Identification Example 4: The O-methylated derivative obtained in the second step reaction is a dia consisting of syn (2S, 3R) / anti (2S, 3S) = 40/60 (area ratio) It is a stereomer mixture, and diastereomer mixture-2 obtained in the third step reaction is syn- (2S, 3R)
-2- (4-hydroxybenzoyloxy) -7-ethoxy-3-methoxy-1,1,1-trifluoroheptane and anti- (2S, 3S) -2- (4-hydroxybenzoyloxy) -7-ethoxy -3-Methoxy-1,1,1-trifluoroheptane, and its formation ratio syn isomer (2S, 3R) type / anti isomer (2S,
Identification of being a mixture of diastereomers of 3S) type = 40/60 (area ratio)]

In a four-necked round-bottomed flask equipped with a thermometer, a stirrer, a reflux condenser, and a funnel, 2.27 g (5 mmol) of the O-methylated derivative obtained in the second step reaction of Reference Example 6.
Then, 25 ml of 3 N hydrochloric acid and 100 ml of methanol were added, and while stirring, the temperature was raised to 80 ° C., and the mixture was refluxed for 6 hours,
The hydrolysis reaction was carried out. Then, after cooling to room temperature,
The mixture is extracted with ether, and the extract is washed with a 20% aqueous solution of sodium carbonate and then with water, and then anhydrous magnesium sulfate is added to remove water, and then the solvent is distilled off under reduced pressure to give a colorless and transparent liquid product [Yield 0.98 g (4 mmol)
The yield is 80%].

Of this product¹H NMR spectrum, 1R
Measurement results of absorption spectrum and MS spectrum are identified
Consistent with Example 2, the product is 2-hydroxy-7-ethoxy
-3-Methoxy-1,1,1-trifluoroheptane
there were. Of the obtained product¹⁹Measure FNMR spectrum
As a result, two peaks are observed, and the position of each peak and
The area ratio is as follows.¹⁹ F NMR spectrum (from ext. CF₃C
OOH) 1st peak: -2.12 ppm, area ratio 40% [syn
Body (2S, 3R) type ☆ 9] Second peak: -4.14 ppm, area ratio 60% [ant
i body (2S, 3S) type ☆ 9] (☆ 9, confirmed by this identification example)

The above product was subjected to optically active gas chromatography under the same conditions as in Identification Example 2 of Reference Example 5. Fig. 13 is a chart of optically active gas chromatography. From the analysis results of the chart in FIG. 13, two optically active peaks are observed, and the retention time and the area ratio of each peak are as follows. 1st peak: retention time 14.55 minutes, area ratio 40% [s
yn body (2S, 3R) type ☆ 10] Second peak: retention time 15.27 minutes, area ratio 60% [a
nti body (2S, 3S) type ☆ 10]

Based on the results of Identification Example 2 of Reference Example 5, the first
The peak (retention time 14.55 min) is syn- (2S, 3
R) -2-hydroxy-7-ethoxy-3-methoxy-
1,1,1-trifluoroheptane, second peak (retention time 15.27 min) is anti- (2S, 3S)
-2-hydroxy-7-ethoxy-3-methoxy-1,
It is confirmed to be 1,1-trifluoroheptane,
The product is syn- (2S, 3R) -2-hydroxy-7
Consisting of -ethoxy-3-methoxy-1,1,1-trifluoroheptane and anti- (2S, 3S) -2-hydroxy-7-ethoxy-3-methoxy-1,1,1-trifluoroheptane, Generation ratio syn body (2
S, 3R) / anti body (2S, 3S) = 40/6
It could be confirmed that this was a mixture of diastereomers consisting of 0 (area ratio).

Syn- (2S, 3R) -2-hydroxy-7-ethoxy-3-methoxy-1,1,1-trifluoroheptane The first peak of the ¹⁹ F NMR spectrum of the product having the same area ratio (- 2.12 ppm) is syn-
(2S, 3R) -2-hydroxy-7-ethoxy-3-
It was confirmed that it may be methoxy-1,1,1-trifluoroheptane. anti-(2S, 3S)
-2-hydroxy-7-ethoxy-3-methoxy-1,
The second peak (-4.14p) of the ¹⁹ F NMR spectrum of the product having the same area ratio as that of 1,1-trifluoroheptane
pm) is anti- (2S, 3S) -2-hydroxy-
It was confirmed to be 7-ethoxy-3-methoxy-1,1,1-trifluoroheptane.

Accordingly, since the absolute configuration of the asymmetric carbon atoms at positions 2 and 3 of the product obtained by hydrolysis of the O-methylated derivative and the O-methylated derivative is not changed,
-Area ratio 40 of ¹⁹ F NMR spectrum of methylated derivative
% Peak (-2.20 ppm) is a syn isomer (2S, 3 R) type, and the second peak (−3.90 ppm) in the ¹⁹ F NMR spectrum has an area ratio of 60% is an
It turned out that it is ti body (2S, 3S) type, and the O-methylated derivative is a diastereomer consisting of syn body (2S, 3R) type / anti body (2S, 3S) type = 40/60 (area ratio) It could be confirmed that it was a mer mixture.

Next, the diastereomer mixture-2 obtained in the third step reaction was subjected to optically active liquid chromatography under the same conditions as in Identification Example 2 of Reference Example 5. The chart of the optically active liquid chromatography is as shown in FIG. 14. From the analysis result of FIG. 14, two optically active peaks were obtained, and the retention time and the area ratio were as follows. First peak: [syn- (2S, 3R) -2- (4-hydroxybenzoyloxy) -7-ethoxy-3-methoxy-1,1,1-trifluoroheptane ☆ 11] retention time: 10.11 minutes Area ratio 40% Second peak: [anti- (2S, 3S) -2- (4-)
Hydroxybenzoyloxy) -7-ethoxy-3-methoxy-1,1,1-trifluoroheptane * 11] Retention time: 11.46 minutes, area ratio 60% (* 11 confirmed from this identification example)

Incidentally, syn body (2S, 3R) type / ant
Diastereomeric mixture by reducing O-methylated derivative which is a diastereomeric mixture consisting of Form i (2S, 3S) = 40/60 (area ratio) with hydrogen gas in the presence of a palladium / carbon catalyst- In the reaction from which 2 is obtained, the configuration of the asymmetric carbon atom at the 2 and 3 positions is irrelevant. Therefore, the syn-isomer of O-methylated derivative (2
The first peak (retention time: 10.11 minutes) of optically active liquid chromatography of diastereomeric mixture-2 corresponding to the area ratio of S, 3R) type is syn- (2S, 3R)-
2- (4-hydroxybenzoyloxy) -7-ethoxy-3-methoxy-1,1,1-trifluoroheptane, while the anti form of O-methylated derivative (2S,
Diastereomeric mixture consistent with area ratio of 3S) type
The second peak of the optically active liquid chromatography of No. 2 (retention time 11.46 minutes) is anti- (2S, 3S) -2
It was found to be-(4-hydroxybenzoyloxy) -7-ethoxy-3-methoxy-1,1,1-trifluoroheptane.

Thus, ^{19 of} diastereomeric mixture-2
The first peak (-1.86 ppm), which has an area ratio of 40% in the FNMR spectrum, is syn- (2S, 3R) -2-
(4-hydroxybenzoyloxy) -7-ethoxy-
The second peak (−2.33 p) which is 3-methoxy-1,1,1-trifluoroheptane and has an area ratio of 60%
pm) was confirmed to be anti- (2S, 3S) -2- (4-hydroxybenzoyloxy) -7-ethoxy-3-methoxy-1,1,1-trifluoroheptane; 2 is syn- (2S,
3R) -2- (4-hydroxybenzoyloxy) -7
-Ethoxy-3-methoxy-1,1,1-trifluoroheptane and anti-2- (4-hydroxybenzoyloxy) -7-ethoxy-3-methoxy-1,1,-
It consists of 1-trifluoroheptane, and its production ratio sy
n-body (2S, 3R) type / anti body (2S, 3S) type =
It could be confirmed that the mixture was a 40/60 (area ratio) diastereomer mixture.

(Fourth stage reaction) [syn- (2S, 3R)
-2- (4-hydroxybenzoyloxy) -7-ethoxy-3-methoxy-1,1,1-trifluoroheptane and anti- (2S, 3S) -2- (4-hydroxybenzoyloxy) -7-ethoxy Preparation of -3-methoxy-1,1,1-trifluoroheptane] Diastereomer mixture-2 obtained in the third step reaction-2,
Under the same conditions as in the fourth step reaction of Reference Example 5, 2.91 g (8 mmol) of the first peak and the second peak were fractionated respectively using silica gel column chromatography, and the eluent was distilled off under reduced pressure. The first fraction [a yield of 1.05 g (2.
A millimole yield of 36%] and a second fraction [yield 1.57 g (4.32 millimoles) 54%] were obtained respectively.

The ¹ H NMR spectrum, 1 R absorption spectrum, and MS spectrum of these target products are in agreement with diastereomer mixture 2, and each target product is 2- (4- (4-)
Hydroxybenzoyloxy) -7-ethoxy-3-methoxy-1,1,1-trifluoroheptane.
The ¹⁹ F NMR spectrum is as follows, and one peak was observed for each. Furthermore, when optically active liquid chromatography was applied under the same conditions as in the fourth step reaction of Reference Example 5, charts similar to FIGS. 11 and 12 were obtained. From the above results, the first fraction, which is the target product, is s
yn- (2S, 3R) -2- (4-hydroxybenzoyloxy) -7-ethoxy-3-methoxy-1,1,1
-Trifluoroheptane, the second fraction is a
nti- (2S, 3S) -2- (4-hydroxybenzoyloxy) -7-ethoxy-3-methoxy-1,1,
It could be confirmed that this was 1-trifluoroheptane.

First fraction [syn- (2S, 3
R) -2- (4-hydroxybenzoyloxy) -7-
Ethoxy-3-methoxy-1,1,1-trifluoroheptane] Retention time 25.30 to 32.30 minutes Yield 1.05 g (2.88 mmol), yield 36
% ¹⁹ F NMR spectrum (from ext. CF ₃ C
OOH) -1.86 ppm Optically active liquid chromatography Retention time 10.11 minutes Second fraction [anti- (2S, 3S) -2-
(4-hydroxybenzoyloxy) -7-ethoxy-
3-methoxy-1,1,1-trifluoroheptane] retention time 34.25 to 44.25 minutes yield 1.57 g (4.32 mmol) yield 54
% ¹⁹ F NMR spectrum (from ext. CF ₃ C
OOH) -2.33 ppm Optically active liquid chromatography Retention time 11.46 minutes

[0092]Example 1[Syn- (2S, 3R) -2-
{4- [4- (4 -N-decylphenyl) benzoyl io
Xy] benzoyloxy} -7-ethoxy-3-methoxy
Production of chi-1,1,1-trifluoroheptane] Equipped with a thermometer, a stirrer, a reflux condenser and a dropping funnel
In a 4-neck round bottom flask, the syn- obtained in Reference Example 5
(2S, 3R) -2- (4-hydroxy benzoyl ester
C) -7-Ethoxy-3-methoxy-1,1,1-tri
1.46 g (4 mmol) of fluoroheptane, 4-
1.62 g of (4-n-decylphenyl) benzoic acid (4.
8 mmol), N, N-dimethylaminopyridine 0.
29 g (2.4 mmol) and methylene chloride 120 m
The solution was stirred at room temperature to prepare a homogeneous solution. Next
Dicyclohexyl carbodiimide in a dropping funnel 1.
Add 22 g (6 mmol), add dropwise with stirring,
Next, keep stirring at room temperature for 5 hours to complete the reaction.
The

After completion of the reaction, precipitated white crystals of dicyclohexylurea are removed by filtration, and the filtrate is diluted with 1N hydrochloric acid, 1
After washing with 0% aqueous sodium hydrogen carbonate solution and then with water,
Anhydrous magnesium sulfate was added to remove water, and then the solvent was evaporated under reduced pressure to remove methylene chloride to obtain a syrupy residue. The residue was dissolved in hot n-hexane and then crystallized by cooling to obtain white crude crystals. The resulting crude crystals are purified by liquid chromatography [eluent n-hexane / isopropyl alcohol = 93/7 (volume ratio)] to give a colorless, transparent, liquid target product [yield: 2.33 g (3.4 mmol) The yield is 85%].

Of this target product¹H NMR spectrum,
¹⁹F NMR spectrum, 1R absorption spectrum and MS
The results of measuring the spectrum are as follows.
The object is 2- {4- [4- (4) -N-decylphenyl) ben
Zoyloxy] benzoyloxy} -7-ethoxy-3
-Methoxy-1,1,1-trifluoroheptane
The Also, this target product is two asymmetric carbons of the starting compound
It is unrelated to the configuration of the element atom, and is optically active
Since the heart does not change, the compound of the present invention syn- (2
S, 3R) -2- {4- [4- (4) -N-decyl pheny
Le) Benzoyloxy] Benzoyloxy} -7-Eto
Xyl-3-methoxy-1,1,1-trifumeorohepta
Was confirmed. Further, from the identification example described later,
It confirmed that it was a syn body (2S, 3R) type.

¹ H NMR spectrum (CDCl ₃ ) 0.8 to 1.04 ppm (6 H), 1.09 to 1.62
ppm (24H), 2.07 to 2.20 ppm (2
H), 2.60 ppm (3 H), 3.07 to 3.20 p
pm (2H), 4.15 to 4.20 ppm (1H),
4.52 to 4.56 ppm (1H), 6.58 to 8.0
4 ppm (12 H) ¹⁹ F NMR spectrum (from ext. CF ₃ C
OOH)-4.95 ppm 1R absorption spectrum (neat) 1,120 cm ^-1 (COC), 1,730 cm ^-1 (CO
O) MS spectrum m / z 684 (M ⁺ ) Also, a ¹ H NMR spectrum is shown in FIG.

(Identification example) [The compound of the present invention is syn- (2
S, 3R) -2- {4- [4- (4) -N-decyl pheny
Le) Benzoyloxy] Benzoyloxy} -7-Eto
Xy-3-methoxy-1,1,1-trifluorohepta
Identification of being a water heater] A thermometer, a stirrer, a reflux condenser, a four-piece equipped with a dropping funnel
Raw material compound 0.36 g (1 millimole) in a round bottom flask
And 5 mmol of 3 N hydrochloric acid and 20 ml of methanol.
Heat to 80 ° C and reflux for 6 hours to carry out hydrolysis reaction
The Then, after cooling to room temperature, ether extraction and extraction
The effluent is washed with 20% aqueous sodium carbonate solution and then with water
After washing with water, add anhydrous magnesium sulfate to
After removal, the solvent is distilled off under reduced pressure to produce a colorless and transparent liquid.
1 [yield 0.2 g (0.8 mmol) yield 80%]
I got

¹ H NMR spectrum of this product-1,
¹⁹ F NMR spectrum, 1R absorption spectrum and MS
The results of measuring the spectrum are as follows.
1 is 2-hydroxy-7-ethoxy-3-methoxy-
It was 1,1,1-trifluoroheptane. ¹ H NMR spectrum (CDCl ₃ ) 0.80 to 1.00 ppm (3 H), 1.04 to 1.3
0 ppm (6 H), 2.48 to 2.64 ppm (3
H), 2.69 ppm (3H), 2.84 to 3.00 p
pm (1 H), 3.12 to 3.26 ppm (2 H),
3.77 to 3.90 ppm (1 H), 4.02 to 4.1
4 ppm (1 H) ¹⁹ F NMR spectrum-2.12 ppm 1 R absorption spectrum (neat) 1,120 cm ^-1 (COC), 1,670 cm ^-1 (O
H) MS spectrum m / z 244 (M ⁺ ) Also, a ¹ H NMR spectrum is shown in FIG.

Then, under the following conditions, the above-mentioned product-1:
It was applied to gas chromatography (hereinafter referred to as optically active gas chromatography) having an optical isomer separation column. Column: trade name Cyclodex β 236 M (manufactured by Chrompack): size ID 0.25 mm, length 25 m: silica capillary column Column temperature: 100 ° C. × 10 minutes and then raised to 200 ° C. at a heating rate of 4 ° C./min Warm carrier gas: Helium, gas flow rate 60 Nl / min, split ratio 10 0/1 Detection: FID

A chart of optically active gas chromatography is shown in FIG. One optically active peak was observed from the analysis result of FIG. 17, and the retention time was 14.55 minutes. The product-1 obtained by hydrolyzing the starting compound has only one optical activity and thus the product is sy.
n- (2S, 3R) -2-hydroxy-7-ethoxy-
It was found to be 3-methoxy-1,1,1-trifluoroheptane. Then, 0.36 g of the raw material compound (1
0.68 g (1 ppm) of the desired product instead of ppm)
The hydrolysis reaction is carried out in the same manner as described above except that a colorless and transparent liquid product-2 [yield 0.2 g (0.
8 mmol) yield 80%] was obtained. As a result of measuring various spectra of this product-2, it is the same as the product-1, and 2-hydroxy-7-ethoxy-3-methoxy-
It was 1,1,1-trifluoroheptane.

In addition, the same conditions as above for the above product-2
And one with optical activity gas chromatography
The optically active peak of is obtained with a retention time of 14.55.
Product-2 is similar to product-1 and syn-
(2S, 3R) -2-hydroxy-7-ethoxy-3-
It is methoxy-1,1,1-trifluoroheptane
The Therefore, even if the target product is hydrolyzed,
From the fact that the absolute configuration of the asymmetric carbon atom at position 3 does not change,
It is determined that the target product is syn (2S, 3R) type
The present compound syn- (2S, 3R) -2- {4
-[4- (4 -N-decylphenyl) benzoyl ester
ベ ン ゾ イ ル] Benzoyloxy} -7-ethoxy-3-methoxy
Confirmed to be -1,1,1-trifluoroheptane
done.

Test Example 1 (Measurement of phase transition temperature of the compound of the present invention) The phase transition temperature of the compound of the present invention was measured by observing the electric field response of the liquid crystal display element described later with a polarizing microscope. It is as follows. However, cry: crystal phase, S
_CA ☆: antiferroelectric liquid crystal phase, SA: smectic A phase and ISO: isotropic liquid phase. The upper value is 4 ° C
When the temperature is raised at / min, the lower value represents the phase transition temperature when the temperature is lowered at 4 ° C./min. Phase transition temperature:

[0102]

[Chemical formula 6]

Thus, the compound of the present invention was an antiferroelectric liquid crystal compound including around room temperature. (Preparation of Liquid Crystal Display Element) An alignment film spin-coated with polyimide is rubbed on two glass substrates with transparent electrodes, and the gap distance is 1.7 um so that the rubbing directions are parallel to each other. The cells were assembled by bonding. The compound of the present invention obtained in Example 1 was injected into the cell obtained above as an isotropic liquid phase. Then, it was gradually cooled to a liquid crystal state. This liquid crystal cell is placed between a polarizer and an analyzer whose transmission axes are orthogonal, and placed so that the normal direction of the molecular layer in the chiral smectic C phase coincides with the direction of the polarizer or analyzer, and no electric field is applied. The third time (0 V)
A liquid crystal display device capable of displaying dark and light was produced by setting the stable state to a dark state and changing it to a chiral smectic C phase by applying an electric field and using that state as a bright state. That is, when the applied voltage was 0 V, the angle of the cell to the polarizer was adjusted so as to minimize the amount of transmitted light. The transmitted light amount was 100% when the transmission axis of the analyzer was rotated to coincide with the transmission axis of the polarizer.

(Evaluation of Liquid Crystal Display Element) Using the liquid crystal display element prepared above, an applied voltage of ± 8.7 at 25 ° C.
FIG. 18 shows a diagram in which the change in the amount of transmitted light with respect to V is measured.
It became. From the figure, a double hysteresis curve was obtained showing one dark state and two bright states. Moreover, the result of having evaluated the performance of the liquid crystal display element by the transmitted light amount change with respect to the applied voltage change in 25 degreeC was as follows. Response time: 28.2us (time to change from bright state to dark state at 25 ° C) Threshold voltage: 5.12 V / um (voltage to be fully bright state at 25 ° C) Tilt angle: 30.20 As a result, the compound of the present invention has an antiferroelectric liquid crystal phase near room temperature, and a liquid crystal display element using it A double hysteresis curve with three stable states at 25 ° C, fast response time, low threshold voltage, large tilt angle, and excellent antiferroelectric liquid crystal compound as large screen display material etc. Was confirmed.

[0105]

The present invention provides an antiferroelectric liquid crystal compound comprising a novel syn- (2S, 3R) -7-ethoxy-3-methoxyheptane derivative having two adjacent asymmetric carbon atoms. An antiferroelectric liquid crystal phase is expressed at around room temperature, and a liquid crystal display device using it has a double hysteresis curve with three stable states, has high-speed response, high tilt angle and low threshold voltage. The liquid crystal compound suitable as a large screen liquid crystal display material etc. is obtained.

Brief Description of the Drawings

1 is 1-hydroxy-2,2,2 obtained in Reference Example 3. FIG.
2-trifluoroethyl-4-ethoxybutyl ketone
^{It is a 1} H NMR spectrum figure.

FIG. 2 is a chart of optically active gas chromatography of an enantiomeric mixture of 1-hydroxy-2,2,2-trifluoroethyl-4-ethoxybutyl ketone obtained in Identification Example 1 in Reference Example 3; .

[FIG. 3] (S) -1-obtained in Identification Example 1 in Reference Example 3
1 is a chart of optically active gas chromatography of hydroxy-2,2,2-trifluoroethyl-4-ethoxybutyl ketone.

FIG. 4 is a ¹ H NMR spectral diagram of 2- (4-benzyloxybenzoyloxy) -7-ethoxy-1,1,1-trifluoroheptanone-3 obtained in Reference Example 4;

[FIG. 5] 7 obtained in Identification Example 1 of the first step reaction of Reference Example 5
-Ethoxy-1,1,1-trifluoroheptane-2,
It is a < ¹ > H NMR spectrum figure of 3-diol.

FIG. 6 is an identification example 1 of the first step reaction of Reference Example 5
2,2-Dimethyl-4- (4-ethoxybutyl) -5-
Trifluoromethyl-1,3-dioxolane  ¹HN
It is a MR spectrum figure.

[Fig. 7] 2- (4-H) obtained in the third step reaction of Reference Example 5
Droxybenzoyloxy) -7-ethoxy-3-meth
Of xyl-1,1,1-trifluoroheptane  ¹HNM
It is R spectrum figure.

[FIG. 8] 2 obtained in Identification Example 2 of the third step reaction of Reference Example 5
-Hydroxy-7-ethoxy-3-methoxy-1,1,
It is a ¹ H NMR spectrum figure of 1-trifluoro heptane.

[FIG. 9] Identification Example 3 of the third step reaction of Reference Example 5
yn- (2S, 3R) -2-hydroxy-7-ethoxy-3-methoxy-1,1,1-trifluoroheptane and anti- (2S, 3S) -2-hydroxy-7-
It consists of ethoxy-3-methoxy-1,1,1-trifluoroheptane, and its formation ratio syn form (2S, 3R)
It is a chart of the optically active gas chromatography of the diastereomer mixture of type / anti body (2S, 3S) type = 70/30 (area ratio).

FIG. 10 is a mixture of diastereomers-1 obtained in the third step reaction of Reference Example 5: syn- (2S, 3R) -2- (4).
-Hydroxybenzoyloxy) -7-ethoxy-3-
Methoxy-1,1,1-trifluoroheptane / ant
i- (2S, 3S) -2- (4-hydroxybenzoyloxy) -7-ethoxy-3-methoxy-1,1,1-
It is a chart of the optically active liquid chromatography of the diastereomer mixture which consists of trifluoro heptane = 70/30 (area ratio).

[FIG. 11] Raw material compound obtained by the fourth step reaction of Reference Example 5: syn- (2S, 3R) -2- (4-hydroxybenzoyloxy) -7-ethoxy-3-methoxy-1,
It is a chart of an optically active liquid chromatography of 1, 1-trifluoro heptane.

[FIG. 12] anti- obtained in the fourth step reaction of Reference Example 5
It is a chart of an optically active liquid chromatography of (2S, 3S) -2- (4-hydroxybenzoyloxy) -7-ethoxy-3-methoxy-1,1,1-trifluoroheptane.

[FIG. 13] Identification of third step reaction of Reference Example 6 syn- (2S, 3R) -2-hydroxy-7-ethoxy-3-methoxy-1,1,1-trifluoroheptane obtained in Example 4 and anti- (2S, 3S) -7-ethoxy-3-
It consists of methoxy-1,1,1-trifluoroheptane, and its formation ratio syn form (2S, 3R) type / anti
It is a chart of the optically active gas chromatography of the diastereomer mixture of body (2S, 3S) type = 40/60 (area ratio).

[FIG. 14] Identification of the diastereomeric mixture obtained in Example 4 of the third step reaction of Reference Example 6: syn- (2S, 3R)
-2- (4-hydroxybenzoyloxy) -7-ethoxy-3-methoxy-1,1,1-trifluoroheptane / anti- (2S, 3S) -2- (4-hydroxybenzoyloxy) -7-ethoxy -3-Methoxy-
It is a chart of the optically active liquid chromatography of the diastereomer mixture which consists of 1, 1, 1- trifluoro heptane = 40/60 (area ratio).

FIG. 15 shows the syn- (2S, 3R) obtained in Example 1.
-2- {4- [4- (4) -N-decylphenyl) benzo
Yloxy] benzoyloxy} -7-ethoxy-3-
Of methoxy-1,1,1-trifluoroheptane¹HN
It is a MR spectrum figure.

FIG. 16 shows the product 1 obtained in the identification example of Example 1: s
yn- (2S, 3R) -2-hydroxy-7-ethoxy-3-methoxy-1,1,1-trifluoroheptane
^{It is a 1} H NMR spectrum figure.

17 is a chart of optically active gas chromatography of Product-1 obtained in the identification example of Example 1. FIG.

FIG. 18: syn- (2S, 3R) -2- {4- [4-]
(4 -N-decylphenyl) benzoyloxy] benzo
Iroxy} -7-ethoxy-3-methoxy-1,1,
Double Hiss of 1-Trifluoroheptane Liquid Crystal Display Device
It is a terrisis curve.

── ── ── ── ── ──

【Procedure Amendment】

[Submission Date] January 8, 1996

[Procedure amendment 1]

[Name of document to be corrected] statement

[Item name to be corrected] 0017

【Correction method】 Change

[Content of correction]

[0017]

[Chemical formula 5]

[Procedure amendment 2]

[Name of document to be corrected] statement

[Item name to be corrected] 0022

【Correction method】 Change

[Content of correction]

¹ H NMR spectrum of this product, ¹⁹
F NMR spectrum, 1R absorption spectrum, and MS
The results of measuring the spectrum are as follows, and are independent of the configuration of the asymmetric carbon atom of this product, and the product is the starting compound (S) -N- because optical inversion does not occur. It was confirmed that it is (2-hydroxy-3,3,3-triculopropionyl) pyrrolidine. ¹ H NMR spectrum ( CDCl ₃ ) 1.53 to 2.37 ppm (4H, m), 3.21 to
3.88 ppm (4H, m), 4.14 ppm (1 H,
br), 4.58 (1 H, q) ¹⁹ F NMR spectrum (from ext. CF ₃
COOH) −4.2 ppm (d, J = 6.0) 1 R absorption spectrum (neat) 1,640 cm ⁻¹ (CO), 3,330 cm ⁻¹ (O
H) MS spectrum m / z 197 (M ⁺ )

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After completion of the reaction, the reaction solution is neutralized by the addition of a 5% aqueous solution of sodium hydrogen carbonate, and the solvent is distilled off under reduced pressure. A saturated aqueous solution of sodium thiosulfate solution is then added, followed by extraction with ether and extraction with anhydrous magnesium sulfate. The reaction mixture was concentrated to dryness under reduced pressure to give a syrupy residue. The residue is subjected to silica gel column chromatography [eluent n-hexane / isopropyl alcohol = 95/5 (volume ratio)]
To give a colorless, clear liquid O-methylated derivative [yield 5.79 g (12.75 mmol) yield 85%]. As a result of measuring the ¹⁹ F NMR spectrum of the obtained O-methylated derivative, two peaks are recognized, and the position and area ratio of each peak are shown as follows: ¹⁹ F NMR spectrum (from ext. CF ₃
COOH) ^Thus, from 19 FNMR the regular 2 Results and below the spectrum, O- methylated derivatives s yn body (2
S, 3R) / anti body (2S, 3S) = 70/3
It was confirmed that the mixture was a mixture of diastereomers consisting of 0 (area ratio).

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¹ H NMR spectrum (CDCl ₃ ) 0.87 to 0.96 ppm (3 H), 1.09 to 1.5
3 ppm (6 H), 2.60 to 2.72 ppm (2
H), 2.75 ppm (3H), 2.87 to 3.00 p
pm (1 H), 3.27 to 3.42 ppm (2 H),
4.18 to 4.35 ppm (1H), 5.41 ppm
(1H), 6.69 to 7.98 ppm (4H, AB pattern) ¹⁹ F NMR spectrum (from ext. CF ₃
COOH) 1R absorption spectrum (neat) 1,110 cm ⁻¹ (COC), 1,740 cm
⁻¹ (COO), 3,300 cm ⁻¹ (OH), MS spectrum m / z. 364 (M ⁺ ) Also, the ¹ H NMR spectrum is shown in FIG.

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Identification Example 2: The O-methylated derivative obtained by the second step reaction is a dia consisting of syn form (2S, 3R) type / anti form (2S, 3S) type = 70/30 (area ratio) It is a stereomeric mixture, and the diastereomeric mixture-1 obtained in the third step reaction is syn- (2S, 3)
R) -2- (4-hydroxybenzoyloxy) -7-
Ethoxy-3-methoxy-1,1,1-trifluoroheptane and anti- (2S, 3S) -2- (4- hydrine)
Droxybenzoyloxy) -7-ethoxy-3-methoxy-1,1,1-trifluoroheptane composed of syn form (2S, 3R) form / anti form (2)
Identification of the S, 3S) type = 70/30 (area ratio) of diastereomer mixture-1] Example 4 in a four-necked round bottom flask equipped with a thermometer, a stirrer, a reflux condenser, and a funnel. O-methylated derivative 1.82 obtained by the second step reaction of
g (4 mmol), 20 ml of 3N hydrochloric acid and 80 ml of methanol were added, and the temperature was raised to 80 ° C. while stirring,
Reflux for an hour to obtain a hydrolysis reaction. Then, after cooling to room temperature, extract with ether, wash the extract with 20% aqueous sodium hydrogen carbonate solution and then with water, add anhydrous magnesium sulfate to remove water, and then remove the solvent under reduced pressure Colorless, clear liquid product [yield 0.78g
(3.2 mmol) yield 80%] was obtained.

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The chart of optically active gas chromatography is shown in FIG. From the analysis results of the chart in FIG. 9, two optically active peaks are observed, and the retention time and the area ratio of each peak are as follows.

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First fraction [syn- (2S, 3
R) -2- (4-hydroxybenzoyloxy) -7-
Ethoxy-3-methoxy-1,1,1-trifluoroheptane] retention time 25.30 to 32.30 minutes yield 1.95 g (5.36 mmol) yield 63% ¹⁹ F NMR spectrum (from ext. CF ₃
COOH) -1.86 ppm Optically active liquid chromatography: retention time 10.11
Minute second fraction [ anti- (2S, 3S) -2-
(4-hydroxybenzoyloxy) -7-ethoxy-
3-methoxy-1,1,1-trifluoroheptane] retention time 34.25 to 44.25 minutes yield 0.83 g (2.30 mmol) yield 27% ¹⁹ F NMR spectrum (from ext. CF ₃
COOH) -2.33 ppm Optically active liquid chromatography: retention time 11.46
Minutes

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¹ H NMR spectrum of this product-3,
^The results of measurement of ¹⁹ F NMR spectrum and 1 R absorption spectrum are in agreement with those of Identification Example 1 of Reference Example 5, and 7-ethoxy-
It was confirmed to be 1,1,1-trifluoroheptane-2,3-diol. Moreover, as a result of measuring a ¹⁹ F NMR spectrum based on the result of the identification example 1 of the reference example 5,
From the position and area ratio of each peak, product-3 is syn- (2S, 3R) -7-ethoxy-1,1,1-trifluoroheptane-2,3-diol and two peaks are observed. anti- (2S, 3S) -7-ethoxy-1,1,1-trifluoroheptane-2,3-diol, and its formation ratio syn form (2S, 3R) type /
It turned out that it is a diastereomer mixture which consists of anti-form (2S, 3S) type = 40/60 (area ratio). ¹⁹ F NMR spectrum (from ext. CF ₃
COOH) 1st peak: -0.48 ppm, area ratio 40% syn
Body (2S, 3R) type Second peak: -2.21 ppm, area ratio 60% ant
i body (2S, 3S) type Therefore, the reaction product syn body (2S, 3R) type / anti body (2S, 3S) type = 40 obtained in the first step reaction
It could be confirmed that this was a mixture of diastereomers consisting of / 60 (area ratio).

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¹ H NMR spectrum of this product-1,
¹⁹ F NMR spectrum, 1R absorption spectrum and M
The results of measurement of the S spectrum are as follows, and the product-1 is 2-hydroxy-7-ethoxy-3-methoxy-
It was 1,1,1-trifluoroheptane. ¹ H NMR spectrum (CDCl ₃ ) 0.80 to 1.00 ppm (3 H), 1.04 to 1.
30 ppm (6 H), 2.48 to 2.64 ppm (3
H), 2.69 ppm (3H), 2.84 to 3.00 p
pm (1 H), 3.12 to 3.26 ppm (2 H),
3.77 to 3.90 ppm (1 H), 4.02 to 4.1
4 ppm (1 H) ¹⁹ F NMR spectrum (from ext. CF ₃
COOH) -2.12 ppm 1R absorption spectrum (neat) 1,120 cm ^-1 (COC), 1,670 cm
^-1 (OH) MS spectrum m / z 244 (M ⁺ ) Also, a ¹ H NMR spectrum is shown in FIG.

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Thus, the compound of the present invention was an antiferroelectric liquid crystal compound including around room temperature. (Preparation of Liquid Crystal Display Element) An alignment film spin-coated with polyimide was rubbed on two glass substrates with transparent electrodes, and the gap distance of 1.7 μm was set so that the rubbing directions would be parallel to each other. The cells were assembled by pasting together. The compound of the present invention obtained in Example 1 was injected into the cell obtained above as an isotropic liquid phase. Then, it was gradually cooled to a liquid crystal state. This liquid crystal cell is placed between a polarizer and an analyzer whose transmission axes are orthogonal, and placed so that the normal direction of the molecular layer in the chiral smectic C phase coincides with the direction of the polarizer or analyzer, and no electric field is applied. The third time (0 V)
A liquid crystal display device capable of displaying dark and light was produced by setting the stable state to a dark state and changing it to a chiral smectic C phase by applying an electric field and using that state as a bright state. That is, when the applied voltage was 0 V, the angle of the cell to the polarizer was adjusted so as to minimize the amount of transmitted light. The transmitted light amount was 100% when the transmission axis of the analyzer was rotated to coincide with the transmission axis of the polarizer.

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(Evaluation of Liquid Crystal Display Element) Using the liquid crystal display element prepared above, an applied voltage of ± 8.7 at 25 ° C.
FIG. 18 shows a diagram in which the change in the amount of transmitted light with respect to V is measured.
It became. From the figure, a double hysteresis curve was obtained showing one dark state and two bright states. Moreover, the result of having evaluated the performance of the liquid crystal display element by the transmitted light amount change with respect to the applied voltage change in 25 degreeC was as follows. Response time: 28.2 μs (time to change from bright state to dark state at 25 ° C.) Threshold voltage: 5.12 V / μm (voltage which becomes completely bright state at 25 ° C.) Tilt angle: 30. (at 25 ° C., the optical axis is the polarizer angle when the threshold voltage) 20 ° above results, the present invention compound has an antiferroelectric liquid crystal phase at around room temperature, a liquid crystal display using the same The device shows a double hysteresis curve with tristable state at 25 ° C, fast response time, low threshold voltage, and large tilt angle, and is an antiferroelectric liquid crystal compound excellent as a large screen display material etc. It has been confirmed that there is.

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[Fig. 12]

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[Fig. 14]

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[Fig. 15]

Claims (2)

[Claim of claim] 1. Formula (1) embedded imageWherein R represents a linear alkyl group having 6 to 14 carbon atoms
The Syn- (2S, 3R) -2- {4- represented by
[4- (4 -Alkylphenyl) benzoyloxy] bee
Nzyloxy} -7-ethoxy-3-methoxy-1,
1,1-trifluoroheptane. 2. A liquid crystal display device using the compound represented by the formula (1) according to claim 1.