JPS5824545A - Optical resolution of (+-)-1-(1-naphthyl)ethylamine - Google Patents

Abstract

PURPOSE:To carry out the optical resolution of (+ or -)-1-(1-naphthyl)ethylamine useful as an optical resolution agent of ceramic acid, easily, in high purity and yield, by using an optically active cis-2-benzamido-cyclohexanecarboxylic acid as the resolution agent. CONSTITUTION:The optical resolution (+ or -)-1-(1-naphthyl)ethylamine is carried out by treating (+ or -)-1-(1-naphthyl)ethylamine with an optically active cis-2-benzamidocyclohexanecarboxylic acid as the resolution agent. To carry out the optical resolution in high purity and efficiency, it is preferable to use equimolar amount of said resolution agent to the (+ or -)-1-(1-naphthyl)ethylamine. The reaction is carried out in a solvent such as water, methanol, ethanol, 1-propanol, etc.

Description

Detailed Description of the Invention The present invention provides $-1-(1-naphthyl) ethylamine, which is characterized by reacting optically active cis-2-benzamidocyclohexanecarboxylic acid with (to)-1-(1-naphthyl)ethylamine. ) Concerning the optical resolution method of ethylamine.

Optically active 1-(1-naphthyl)ethylamine is widely used as an optical resolving agent for racemic acids, similar to basic natural optical resolving agents such as ephedrine, quinine, or brucine. A simple method for the optical resolution of 1-naphthyl-ethylamine is desired.

Conventionally, as a method for obtaining an optically active form of 1-(1-naphthyl)ethylamine, (method using tartaric acid [Ro
bert R, Bottoms U, S.

2, 996.545 Aug, 5.1957:) or (t)- or (→-method using menthyl phthalate (Robert R, Bottoms U, S
, 3J000.9475ept.

23.1957), but all of them require repeated recrystallization to obtain a pure optically active substance, and the yield cannot be increased.

In order to overcome this difficulty, the present invention aims to (a)-1-(1-
As a result of further intensive research on the optical resolution method of naphthyl)ethylamine, we found that by using optically active cis-2-benzamidocyclohexanecarboxylic acid as a resolving agent, we can obtain high-purity -1-(1-naphthyl)ethylamine. It has been found that optical resolution can be easily performed with high yield.

That is, the present invention forms diastereomeric salts by reacting optically active cis-2-benzamide cyclohexanecarboxylic acid with (th)-1-(1-naphthyl)ethylamine, and utilizes the difference in solubility thereof. This is a method of optical separation.

In the present invention, optically active cis-2-benzamidocyclohexanecarboxylic acid as a resolving agent and (t)-1-(1
Although the molar ratio with -naphthyl)ethylamine is not particularly limited, if the resolving agent is used in an equimolar amount to (t)-1-(1-naphthyl)ethylamine, the output-1-(
1-Naphthyl)ethylamine is preferred because it can be optically resolved efficiently (and with high purity).

In addition, (to)-1-(1-naphthyl)ethylamine and optically active cis-2-benzamidocyclohexanecarboxylic acid are allowed to react in a solvent, and the solvents used at that time include water, methanol, ethanol, By using 1-glopanol, 2-propanol, 1-butanol, 2-butanol, acetone, methyl ethyl ketone, etc. alone or an appropriate mixture thereof,
Highly purified optically active 1-(1-naphthyl)ethylamine is obtained.

The present invention is carried out, for example, in the following manner.

(a)-1-(1-naphthyl) ethylamine in a solvent such as methanol and! r3-1--1・χ-naphthyl)
Equimolar amount of optically active cis-2- to ethylamine
Add benzamide cyclohexane carboxylic acid, heat and dissolve, then cool to make supersaturated, preferably (a)
-1-(1-naphthyl)ethylamine・(c)-cis-
2-benzamide cyclohexanecarboxylate or (
-> A small amount of -1-(1-naphthyl)ethylamine/(t)-cis-2-benzamide cyclohexanecarboxylate is inoculated to precipitate a poorly soluble diastereomeric salt of the same type, which is then separated. The obtained salt is recrystallized if necessary, then treated with a water-soluble base, the liberated amine is extracted with an organic solvent, and then distilled to obtain an optically active (...~
Alternatively, Sakaki-1-(1-naphthyl)ethylamine is obtained.

In addition, the resolving agent that exists as an alkali salt in an aqueous solution is
By treating this aqueous solution with a mineral acid such as hydrochloric acid or sulfuric acid, optically active cis-2-benzamidocyclohexanecarboxylic acid can be recovered.

Next, the present invention will be explained in more detail with reference to Examples.
The scope of the invention is not limited thereby.

Example 1 50 Thimethanol 600-(sub)-1-(1-naphthyl)ethylamine (abbreviated as - below) 17.1
2.9 (100 mmol) and (t)-cis-2
-Benzamidocyclohexanecarboxylic acid [hereinafter (g)
-2]24.73. ! i' (100 mmol
), heat and dissolve, cool to room temperature, stand for 24 hours to precipitate crystals, and filter (→-L-
(a) - Ashishio 17.29. ! 7 (41.3m mol
) was obtained.

By recrystallizing this salt from 50 timethanol 240-
2 mmol) was obtained. The yield based on (-)-1-(1-naphthyl)ethylamine in the used 1-(to)-1-(1-su7f)ethylamine was 70.4%. After adding 200% of a 1N aqueous sodium hydroxide solution and extracting with benzene, the organic layer was distilled under reduced pressure to obtain 5.509 (32.1 mmol) of (c)-1.

Boiling point 115°C/3, OmmHg, yield 64.3%, 8 [α) -62.3° (C=5, methanol), 8
9 Optical purity 100%.

Example 2 50% methanol 600-(a)-117,12Ji
'(100mmo1) and (-)) -224,73&
(100 mmol) was added and dissolved by heating, then cooled to room temperature and allowed to stand for 24 hours to precipitate crystals, which were filtered.

This mother liquor was concentrated, 200% of a 2N aqueous sodium hydroxide solution was added thereto and extracted with benzene, and then the benzene in the organic layer was distilled off.

H-214,50,! in the residue! i' (58,6m m
ol) was added and dissolved by heating in 340 ml of 50-thimethanol. By cooling to room temperature and filtering the precipitated crystals, 17.97 g (42.9 m
mol) was obtained. Add to this 200m7 of 1N sodium hydroxide aqueous solution! was added and extracted with benzene, and the organic layer was distilled under reduced pressure to obtain 6-87 g (40,
1 mmol) of (-1-3-1 was obtained. Boiling point 110°C
/2.5 trrm Hg yield 9 80.2%, (α) +58.7' (C=5, methanol 89 alcohol), optical purity 94.2%.

Example 3 50 Thimethanol 600-117,129 (10
0mmo1) and f-”)-224,739 (100
mmol), heat and dissolve, then cool to room temperature.
By keeping it quiet for 4 hours to precipitate crystals and filtering (
b)-1・[-2 salt 18.649 (44.5m mol
) got '.

By recrystallizing this salt from 50 timeethanol 260-(+)-1-(→-2 salt 15.889 (37
, 9 mmol) was obtained. Usage (a) - Onaka's ←) -
The yield for 1 was 75.9%. After adding 200 mj of 1N sodium hydroxide aqueous solution to this and extracting with benzene, the organic layer was distilled under reduced pressure to obtain 5.91.
9 (34.5 mmol) of (-1-3-1) was obtained. Boiling point 124°C/3.5 l mHg Yield 69.0%, [α) +60.7″
'(c89 = 5, methanol), optical purity 97.4% Patent applicant
Hiroshi Nohira

Claims (1)

[Claims] A method for optical resolution of ffl-1-(1-naphthyl)ethylamine, which comprises reacting (t)-1-(1-naphthyl)ethylamine with optically active cis-2-benzamidocyclohexanecarboxylic acid.