JP2002003453A - METHOD FOR PURIFYING OPTICALLY ACTIVE alpha-METHYL- BIS-3,5-(TRIFLUOROMETHYL) BENZYLAMINES - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for industrially readily and efficiently purifying optically active α-methyl-bis-3,5-(trifluoromethyl)benzylamine of an important intermediate for a medicine and an agrochemical, in high optical purity. SOLUTION: The optically active α-methyl-bis-3,5-(trifluoromethyl) benzylamines are purified so as to have a high optical purity by forming the α-methyl-bis-3,5-(trifluoromethyl)benzylamines into a salt of an organic acid, and recrystallizing the resultant salt.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to an optically active α-methyl-bis-3,5-, an important intermediate of pharmaceuticals and agricultural chemicals.
The present invention relates to a purification method for obtaining (trifluoromethyl) benzylamine with high optical purity.

[0002]

2. Description of the Related Art Optically active α-methyl-bis-3,5-
(Trifluoromethyl) benzylamine is a key intermediate in medicine and pesticides. The method for producing the optically active amine is described in J. Am. Chem. Soc., 112, 5741 (1990).
J. Chem. Soc., Perkin Tran
s. 1, 2039 (1985) with reference to the asymmetric reduction of an oxime derivative. However, its optical purity is moderate at 71% ee (S), and its chemical yield is as low as 15%. An industrially simple and efficient production method for obtaining the optically active amine with high optical purity is not available. Did not.

[0003]

SUMMARY OF THE INVENTION An object of the present invention is to provide an optically active α-methyl-bis-3,5- (trifluoromethyl) benzylamine itself or a synthetic intermediate thereof as a salt of an inorganic acid or an organic acid. To obtain α-methyl-bis-3,5- (trifluoromethyl) benzylamine of high optical purity.

[0004]

Means for Solving the Problems The present inventors have made intensive studies to solve the above-mentioned problems, and as a result, have found that optically active α-methyl-bis-3,5- (trifluoromethyl) benzylamine itself, Alternatively, it is apparent that α-methyl-bis-3,5- (trifluoromethyl) benzylamine having a high optical purity can be obtained by recrystallizing and purifying the synthetic intermediate with a salt of an inorganic acid or an organic acid. I made it.

That is, the present invention provides a compound represented by the general formula [1]:

[0006]

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[Wherein, R represents hydrogen, a benzyl group, an allyl group, or an optically active α-arylethyl group represented by C * HMeAr, Ar represents a phenyl group or 1 or 2-naphthyl group, Represents an asymmetric carbon.] An optically active α-methyl-bis-3,5- (trifluoromethyl) benzylamine represented by the following formula is converted into a salt of an inorganic acid or an organic acid and purified by recrystallization. It is a purification method.

Further, the present invention provides a compound represented by the general formula [1]:

[0009]

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Wherein R represents hydrogen, a benzyl group, an allyl group or an optically active α-arylethyl group represented by C * HMeAr; Ar represents a phenyl group or 1 or 2-naphthyl group; Represents an asymmetric carbon atom], and is a salt of an optically active α-methyl-bis-3,5- (trifluoromethyl) benzylamine with an inorganic or organic acid.

[0011]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, a method for purifying optically active α-methyl-bis-3,5- (trifluoromethyl) benzylamine of the present invention will be described in detail.

The optically active α-methyl-bis-3,5- (trifluoromethyl) benzylamine represented by the general formula [1] of the present invention may be produced by any method. Six compounds represented by the formula can be given. Among them, α-methyl-bis-3,5- (trifluoromethyl) benzylamine itself (1-a), N-benzyl form (1-b), N-α-phenylethyl form (1-
d) is more preferred. * Represents an asymmetric carbon, 1-a,
The stereochemistry of 1-b and 1-c includes R-form and S-form, and those having an optical purity of 10% ee or more can be used. The stereochemistry of 1-d, 1-e, and 1-f includes combinations of RR, SR, RS, and SS (the absolute configuration shown before the hyphen). Is
represents the absolute configuration on the α-methyl-bis-3,5- (trifluoromethyl) benzyl group side, and the absolute configuration shown after the hyphen represents the absolute configuration on the α-arylethyl group side as a chiral auxiliary, Usually, an R-form or S-form chiral auxiliary having 98% ee or more is used), and those having a diastereomer excess of 10% de or more can be used.

[0013]

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Examples of the inorganic acid used in the present invention include carbonic acid, hydrochloric acid, sulfuric acid, nitric acid, hydrobromic acid, hydroiodic acid, phosphoric acid, boric acid, perchloric acid and the like. Among them, hydrochloric acid is more preferred.

The organic acids used in the present invention include acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, isovaleric acid, hexanoic acid, heptanoic acid, cyclohexanecarboxylic acid, octanoic acid, phenylacetic acid, and 3-phenylpropionic acid. Alkyl carboxylic acids such as acids, chloroacetic acid, dichloroacetic acid, trichloroacetic acid, fluoroacetic acid, difluoroacetic acid, trifluoroacetic acid, bromoacetic acid, iodoacetic acid, 2-
Haloalkylcarboxylic acids such as chloropropionic acid and 3-chloropropionic acid, acrylic acid, crotonic acid, citraconic acid, maleic acid, fumaric acid, cis or tra
unsaturated carboxylic acids such as ns-cinnamic acid, benzoic acid,
o, m or p-toluic acid, o, m or p-fluorobenzoic acid, o, m or p-chlorobenzoic acid, o, m
Or p-bromobenzoic acid, o, m or p-iodobenzoic acid, o, m or p-hydroxybenzoic acid, o, m
Or p-anisic acid, o, m or p-aminobenzoic acid, o, m or p-nitrobenzoic acid, o, m or p
-Aromatic carboxylic acids such as cyanobenzoic acid, o, m or p-benzenedicarboxylic acid, α, β or γ-picolinic acid, 2,6-pyridinedicarboxylic acid, 1 or 2-naphthoic acid, methanesulfonic acid, chloro Sulfonic acids such as methanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, p-phenolsulfonic acid, lactic acid, malic acid, tartaric acid, dibenzoyltartaric acid, 2-phenylpropionic acid, mandelic acid, camphoric acid Optically active carboxylic acids such as cis-2-benzamidocyclohexanecarboxylic acid, optically active sulfonic acids such as phenylethanesulfonic acid and 10-camphorsulfonic acid, and 2,2 ′-(1,1′-binaphthyl) phosphoric acid Optically active phosphoric acids, 4-aminobutyric acid, phenylglycine, asparagine Optically active amino acid such as acid, pyroglutamic acid, N- acetyl-3,5-dibromo - tyrosine, N- acyl - Phenylalanine, N- acyl - aspartic acid, N- acyl glutamic acid, N-
Optically active N-acyl amino acids such as acylproline (N
-Acyl groups include acetyl, benzyloxycarbonyl, benzoyl, benzenesulfonyl, p-
Such as formic acid, oxalic acid, malonic acid, succinic acid, adipic acid, pimelic acid, cyanoacetic acid, citric acid, glycolic acid, glyoxylic acid, pyruvic acid, levulinic acid, and the like. Oxaloacetic acid, mercaptoacetic acid, phenoxyacetic acid, picric acid and the like can be mentioned. Optically active carboxylic acids, optically active sulfonic acids, optically active phosphoric acids, optically active amino acids and optically active N-acyl amino acids have optical isomers, and both optical isomers can be used. Among them, p-toluenesulfonic acid, optically active tartaric acid, and optically active mandelic acid are more preferable.

The amount of the acid used in the present invention is as follows:
Optically active α-methyl-bis- represented by the general formula [1]
It may be used in an amount of 0.3 molar equivalent or more based on 3,5- (trifluoromethyl) benzylamine,
Molar equivalents are preferred, especially 0.3 to 2 molar equivalents.

The method for preparing the salt of the present invention may be determined appropriately depending on the combination of the optically active α-methyl-bis-3,5- (trifluoromethyl) benzylamines and the acid. It can be prepared by directly adding and mixing the active amines and the acid, or by preparing respective solutions in advance and mixing the solutions.

The recrystallization solvent used in the present invention includes:
There is no particular limitation as long as it does not react with the optically active α-methyl-bis-3,5- (trifluoromethyl) benzylamines, acids or salts thereof, and optical purity or diastereomeric excess before purification, Alternatively, it may be appropriately determined according to the target optical purity after purification, diastereomer excess ratio, recovery ratio, and the like. Such recrystallization solvents include n-pentane, n-hexane, c-hexane, and n-hexane.
Aliphatic hydrocarbons such as heptane, benzene, toluene,
Ethylbenzene, xylene, aromatic hydrocarbons such as mesitylene, methylene chloride, chloroform, halogenated hydrocarbons such as 1,2-dichloroethane, diethyl ether, tetrahydrofuran, t-butyl methyl ether,
Ethers such as 1,4-dioxane, ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone,
Examples include esters such as ethyl acetate and n-butyl acetate, nitriles such as acetonitrile and propionitrile, alcohols such as methanol, ethanol, n-propanol, i-propanol and n-butanol, and water. Among them, n-hexane, n-heptane, toluene, methylene chloride, t-butyl methyl ether, acetone, ethyl acetate, acetonitrile, methanol, ethanol, and i-propanol are more preferable. These solvents can be used alone or in combination.

The amount of the recrystallization solvent used in the present invention is not particularly limited as long as the salt before purification is completely or partially dissolved when heated. The ratio may be appropriately determined based on the diastereomer excess, the target optical purity after purification, the diastereomer excess, and the recovery rate. Usually, the general formula [1]
The amount of the optically active α-methyl-bis-3,5- (trifluoromethyl) benzylamine may be 1 volume or more, preferably 1 to 100 volumes, more preferably 1 to 50 volumes. Is more preferred.

In the recrystallization operation of the present invention, crystals can be deposited smoothly and efficiently by adding a seed crystal. The amount of the seed crystal used is preferably 1/10 to 1/10000 weight, more preferably 1/20 to 1/1000 weight, based on the salt before purification.

The temperature conditions for the recrystallization operation of the present invention can be appropriately determined depending on the boiling point and the freezing point of the solvent used. Usually, the temperature before room temperature (25 ° C.) is around the boiling point of the recrystallization solvent, Is dissolved, and crystals can be precipitated at -40 to 80 ° C.

In the present invention, since the optical purity or diastereomer excess of the precipitated crystal is improved, the precipitated crystal is recovered by filtration or the like to obtain a high purity α.
-Methyl-bis-3,5- (trifluoromethyl) benzylamines can be obtained. Further, by repeating the recrystallization operation, a product having a higher purity can be obtained. When the obtained salt is the salt of 1-a,
It is possible to recover α-methyl-bis-3,5- (trifluoromethyl) benzylamine of high optical purity by neutralizing with an aqueous alkaline solution such as sodium hydroxide and sodium hydrogen carbonate, and extracting with an organic solvent. it can.

In the case of the salts of 1-b to 1-f, racemization is carried out as a salt or after forming a free base with an alkaline aqueous solution, by a deprotection reaction such as hydrogenolysis. Thus, the objective α-methyl-bis-3,5- (trifluoromethyl) benzylamine having a high optical purity can be obtained. The optically active amine can be recovered as a free base by neutralizing with an aqueous alkaline solution and extracting with an organic solvent. , Distillation, recrystallization, column chromatography and the like.

[0024]

EXAMPLES Hereinafter, embodiments of the present invention will be described specifically with reference to Examples, but the present invention is not limited to these Examples.

The absolute configuration of the optically active α-methyl-bis-3,5- (trifluoromethyl) benzylamine shown in the examples was determined by comparing the sign of the measured optical rotation with the sign of the literature value. . Further, the absolute configuration of the synthetic intermediate was determined by performing a deprotection reaction by hydrogenolysis and converting to an optically active amine. % De and% e in Examples and Reference Examples
e represents a diastereomeric excess and an enantiomeric excess, respectively, and represents chiral GC (CP-Chirasil).
-Dex CB).

[Example 1] Recrystallization purification of / 1-a with p-toluenesulfonate In 6.5 ml of toluene, optically active α-methyl-bis- was added.
3,5- (trifluoromethyl) benzylamine (1-
a, enantiomeric ratio / S-form: R-form = 7.4: 1)
02g (3.97 mmol, 1 eq) and 0.68 g (3.59 mmol, p-toluenesulfonic acid monohydrate)
0.9 eq) and stirred at 60-70 ° C. for 30 minutes,
6 ml of n-hexane was added, and the mixture was allowed to cool to room temperature and left for one day. The precipitated crystals were filtered, washed with a small amount of n-hexane, dried in vacuo, and then 0.20 g of crystals having the structure shown below.
And 1.44 g of mother liquor were obtained. Each ee is 0.5N
-The base was converted to a free base with an aqueous solution of NaOH, and chiral GC analysis revealed that 82.7% ee (major form was S form), 7
It was 4.2% ee (the major body was an S body).

[0027]

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¹ H-NMR (TMS, DMSO):
54 (d, 6.8 Hz, 3H), 2.28 (s, 3
H), 4.69 (q, 6.8 Hz, 1H), 7.10
(D, 8.3 Hz, 2H), 7.46 (d, 8.3H
z, 2H), 8.17 (s, 1H), 8.23 (s, 2H)
H), 8.30 (br, 3H).

[Example 2] Recrystallization and purification of (1-a) with (D) -tartrate salt 30 ml of methanol was added to optically active α-methyl-bis-
3,5- (trifluoromethyl) benzylamine (1-
a, enantiomeric ratio / S-form: R-form = 7.4: 1)
94 g (3.64 mmol, 1 eq) and 0.55 g (3.64 mmol, 1 eq) of (D) -tartaric acid were added, and the mixture was stirred under reflux for 30 minutes, allowed to cool to room temperature, and left for half a day. The precipitated crystals were collected by filtration, washed with a small amount of methanol, and dried in vacuo.
8 g were obtained. Each ee was converted to a free base with a 0.5N-NaOH aqueous solution and subjected to chiral GC analysis. As a result, 91.4% ee (major form was S form) and 43.8%, respectively.
% Ee (major body is S body).

[0030]

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¹ H-NMR (TMS, DMSO):
45 (d, 6.8 Hz, 3H), 3.92 (s, 2
H) 4.52 (q, 6.8 Hz, 1H), 8.08
(S, 1H), 8.19 (s, 2H).

[Example 3] Recrystallization purification of (1 / a) with (S) -mandelic acid salt 3 ml of toluene was added with optically active α-methyl-bis-3,5.
0.64 g of-(trifluoromethyl) benzylamine (1-a, enantiomeric ratio / S-form: R-form = 3.8: 1)
(2.49 mmol, 1 eq) and 0.17 g (1.12 mmol, 0.45 eq) of (S) -mandelic acid were added, and the mixture was stirred under reflux for 30 minutes, added with 1.5 ml of n-hexane, and allowed to cool to room temperature. And left in the refrigerator for 2 days. The precipitated crystals were collected by filtration, washed with a small amount of n-hexane, and dried under vacuum.
8 g were obtained. Each ee was converted to a free base with a 0.5N-NaOH aqueous solution and subjected to chiral GC analysis.
6.1% ee (major body was S body) and 4.7% ee (major body was S body).

[0033]

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¹ H-NMR (TMS, DMSO):
39 (d, 6.8 Hz, 3H), 4.41 (q, 6.8
Hz, 1H), 4.71 (d, 2.0 Hz, 1H),
7.19 (t, 7.3 Hz, 1H), 7.26 (t,
7.3 Hz, 2H), 7.36 (d, 7.3 Hz, 2
H), 8.01 (s, 1H), 8.15 (s, 2H).

[Example 4] Purification of recrystallization of (1 / a) with (S) -mandelic acid salt In 4.5 ml of toluene, optically active α-methyl-bis- was added.
3,5- (trifluoromethyl) benzylamine (1-
a, enantiomeric ratio / S-form: R-form = 8.8: 1)
80 g (3.10 mmol, 1 eq) and 0.47 g (3.09 mmol, 1 eq) of (S) -mandelic acid were added,
The mixture was stirred under reflux for 30 minutes, 1.8 ml of n-hexane was added, and after allowing to cool to room temperature, seed crystals were added and the mixture was allowed to stand for 3 hours.
The precipitated crystals are filtered and washed with a small amount of n-hexane,
After vacuum drying, 0.89 g of crystals having the structure shown below and 0.35 g of mother liquor were obtained. Each ee is 0.5N-Na
It was made into a free base with an aqueous OH solution and subjected to chiral GC analysis. As a result, 90.7% ee (major form was S form), 58.1%
ee (major body is S body).

[0036]

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The ¹ H-NMR spectrum was the same as in Example 3.

Example 5 Purification of recrystallization of (1-a) with (S) -mandelic acid salt To 10 ml of toluene was added optically active α-methyl-bis-3,
(S)-of 5- (trifluoromethyl) benzylamine
Mandelate (1-a · (S) -mandelate, enantiomeric ratio / S-form: R-form = 95.5: 4.5) 0.89
g, stirred at 80 ° C. for 30 minutes, and allowed to cool to room temperature.
Left for 1 hour. The precipitated crystals were collected by filtration, washed with a small amount of toluene, and dried in vacuo.
1 g and 0.18 g of mother liquor were obtained. Each ee is 0.
As a result of chiral GC analysis after making a free base with a 5N-NaOH aqueous solution, 99.7% ee (major form is S form),
It was 82.7% ee (the major body was an S body).

[0039]

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The ¹ H-NMR spectrum was the same as in Example 3.

[Example 6] Purification of recrystallization with hydrochloride salt of / 1-d Optically active α-methyl-bis-
3,5- (trifluoromethyl) benzylamines (1
-D, diastereomer ratio / SS form: RS form = 7.
5: 1) 2.32 g (6.43 mmol) was dissolved, and 10% hydrochloric acid methanol was added in excess under ice-cooling.
After stirring for 0 minutes, concentration and drying in vacuo, a crude product of the hydrochloride salt of 1-d was obtained in a quantitative yield. 30 ml of a mixed solution (50: 1) of n-hexane-ethanol was added to the crude product,
The mixture was stirred and washed at 50 ° C. for 30 minutes, allowed to cool to room temperature, and left overnight. The precipitated crystals were filtered, washed with a small amount of n-hexane, dried in vacuo, and then 1.98 g of crystals having the structure shown below.
And 0.58 g of mother liquor. Each de is 0.5N
-The base was converted to a free base with an aqueous solution of NaOH and analyzed by chiral GC.
(S-form), 54.7% de (major form is S-S form).

[0042]

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¹ H-NMR (TMS, DMSO):
58 (d, 6.8 Hz, 3H), 1.62 (d, 6.8
Hz, 3H), 3.99 (q, 6.8 Hz, 1H),
4.28 (q, 6.8 Hz, 1H), 7.25-7.4
8 (m, 5H), 8.13 (s, 3H), 10.22
(Br, 1H), 10.53 (br, 1H).

Example 7 Purification of recrystallization of p-toluenesulfonic acid salt of / 1-d in 42 ml of t-butyl methyl ether was added an optically active α-methyl-bis-3,5- (trifluoromethyl) benzylamine (1-d, diastereomer ratio / SS form: R)
-S form = 7.5: 1) 3.04 g (8.42 mmol,
1eq) and p-toluenesulfonic acid monohydrate 1.60
g (8.42 mmol, 1 eq) at 40.degree.
After stirring for 72 minutes, 72 ml of n-hexane was added, and after allowing to cool to room temperature, seed crystals were added and left overnight. The precipitated crystals were filtered, washed with a small amount of n-hexane, and dried under vacuum to obtain 3.12 g of crystals having the structure shown below and 1.37 g of mother liquor.
Each de was converted to a free base with a 0.5N-NaOH aqueous solution and subjected to chiral GC analysis.
3% de (major body is SS body), 16.6% de
(The major body was an SS body).

[0045]

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¹ H-NMR (TMS, DMSO):
55 (d, 6.0 Hz, 3H), 1.58 (d, 6.0
Hz, 3H), 2.28 (s, 3H), 4.29 (q,
6.0 Hz, 1H), 4.54 (q, 6.0 Hz, 1H)
H), 7.11 (d, 8.0 Hz, 2H), 7.38
(M, 2H), 7.43 (m, 3H), 7.47 (d,
8.0 Hz, 2H), 8.10 (s, 2H), 8.20
(S, 1H), 9.41 (br, 2H).

[Example 8] Purification of recrystallization of (1-d) with (S) -mandelic acid salt. To 1 ml of toluene, optically active α-methyl-bis-3,5 was added.
-(Trifluoromethyl) benzylamines (1-d,
Diastereomer ratio / SS form: RS form = 7: 1)
0.81 g (2.23 mmol, 1 eq) and (S) -mandelic acid 0.34 g (2.23 mmol, 1 eq) were added, and the mixture was stirred at 60 ° C. for 30 minutes, added with n-hexane 6 ml, and allowed to cool to room temperature. , Left overnight. The precipitated crystals were filtered, washed with a small amount of n-hexane, and dried under vacuum to obtain 0.99 g of crystals having the structure shown below and 0.12 g of mother liquor.
Each de was converted to a free base with a 0.5N-NaOH aqueous solution and subjected to chiral GC analysis.
2% de (major body is SS body), 57.8% de
(The major body was an SS body).

[0048]

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¹ H-NMR (TMS, DMSO):
19 (d, 6.4 Hz, 3H), 1.23 (d, 6.4
Hz, 3H), 3.29 (q, 6.4 Hz, 1H),
3.60 (q, 6.4 Hz, 1H), 4.99 (s, 1
H), 7.07-7.46 (m, 10H), 7.92
(S, 2H), 7.94 (s, 1H).

Reference Example 1 Optically active α-methyl-bis-3,5 of purified 1-dp-toluenesulfonic acid salt
Conversion to-(trifluoromethyl) benzylamine In 50 ml of toluene, p-toluenesulfonic acid of optically active α-methyl-bis-3,5- (trifluoromethyl) benzylamine purified with reference to Example 7 Salt (1
-D.p-toluenesulfonate, 99.6% de, major form is SS form) 13.3 g (24.95 mmo)
1, 1 eq) and 100 ml of 0.5N-NaOH aqueous solution
(50 mmol, 2 eq), and the mixture was stirred at room temperature for 30 minutes. After static separation, the recovered aqueous layer was extracted with toluene, and the combined recovered organic layers were washed with saturated saline and dried over anhydrous sodium sulfate. After filtration, concentration and vacuum drying, 1-d having the structure shown below was obtained in a quantitative yield.

[0051]

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The obtained 1-d was dissolved in 26 ml of methanol, and 5% palladium / activated carbon (containing 50% by weight of water) was added.
45 g (5% by weight) was added, the hydrogen pressure was set to 0.2 MPa, and the mixture was stirred at 60 ° C for 22 hours. The reaction-terminated liquid is filtered through celite, concentrated, and dried under vacuum.
The crude product of -1-a was obtained in a quantitative yield. The crude product is
Purification by simple distillation (96-97 ° C / 31 mmHg) was performed to obtain 5.41 g of a high-purity product (total yield of two steps is 84%). GC purity and ee were 9
9.4% and 99.4% ee.

[0053]

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[0054]

Industrial Applicability The optically active α-methyl-bis-3,5- (trifluoromethyl) benzylamine, which is an important intermediate of pharmaceuticals and agricultural chemicals, can be industrially simply and efficiently purified to high optical purity.

 ──────────────────────────────────────────────────続 き Continued on the front page (72) Inventor Manabu Yasumoto 2805 Imafukunakadai, Kawagoe-shi, Saitama Prefecture Central Research Institute of Glass Co., Ltd. (72) Inventor Masatomi Kanai 2805 Imafukunakadai, Kawagoe-shi, Saitama Central Inside Glass Chemical Company (72) Inventor Takashi Hayami 2805 Imafukunakadai, Kawagoe City, Saitama Prefecture Central Glass Company Chemical Laboratory F-term (reference) 4H006 AA02 AC83 AD15 AD33 BB11 BB14 BB15 BC10 BC19 BC51

Claims (8)

[Claims] 1. A compound of the general formula [1] Wherein R is hydrogen, benzyl, allyl or C *
Represents an optically active α-arylethyl group represented by HMeAr, Ar represents a phenyl group or 1 or 2-naphthyl group, and * represents an asymmetric carbon]. , 5- (trifluoromethyl)
A refining method comprising converting a benzylamine into a salt of an inorganic acid or an organic acid and recrystallizing the same. 2. The purification method according to claim 1, wherein the inorganic acid is hydrochloric acid. 3. The method according to claim 1, wherein the organic acid is selected from the group consisting of p-toluenesulfonic acid, optically active tartaric acid, and optically active mandelic acid. 4. The purification method according to claim 1, wherein the stereochemistry of * in the general formula [1] is R-form or S-form. 5. A compound of the general formula [1] Wherein R is hydrogen, benzyl, allyl or C *
Represents an optically active α-arylethyl group represented by HMeAr, Ar represents a phenyl group or 1 or 2-naphthyl group, and * represents an asymmetric carbon]. , 5- (trifluoromethyl)
Salts of benzylamines with inorganic or organic acids. 6. The salt according to claim 5, wherein the inorganic acid is hydrochloric acid. 7. The salt according to claim 5, wherein the organic acid is selected from the group consisting of p-toluenesulfonic acid, optically active tartaric acid, and optically active mandelic acid. 8. The salt according to claim 5, wherein the stereochemistry of * in the general formula [1] is R-form or S-form.