Method for preparing D-serine by kinetic resolution

A kinetic resolution, serine technology, applied in chemical instruments and methods, cyanide reaction preparation, preparation of organic compounds, etc., to achieve the effect of improving the separation yield, reducing operating costs, and stable product quality

Active Publication Date: 2010-06-16
SHANGHAI SHISI CHEM PROD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, this classic resolution method can only resolve half of the D-form in DL-serine

Method used

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  • Method for preparing D-serine by kinetic resolution
  • Method for preparing D-serine by kinetic resolution

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] (1) Preparation of DL-serine methyl ester:

[0028] Add 84.0g (0.80mol) DL-serine, 400ml anhydrous methanol and 252.0g Amberlyst-15 ion exchange resin to the reactor with stirring, heating and thermometer, heat up to 65°C while stirring, and maintain the temperature React for 1 hour. The reaction solution was cooled to room temperature, filtered, and reused after the filtrate was recovered, and the solid phase was adjusted to pH=8 with 30% ammonia water, extracted 3 times with each 200ml ethyl acetate solvent, and the ethyl acetate solvent was evaporated (recycled after solvent recovery) ) to obtain 91.6 g of DL-serine methyl ester, with a yield of 96.2% and a purity of 99.36% (HPLC).

[0029] (2) Preparation of D-serine methyl ester L-DBTA di-salt:

[0030] Add respectively the DL-serine methyl ester that 23.8g (0.20mol) step (1) obtains in the reactor with stirring, heating, thermometer, 50ml methanol, 1.1g (0.01mol) 2-formylpyridine, while stirring Heat up to 60°C...

Embodiment 2

[0034] (1) Preparation of DL-serine methyl ester is the same as in Example 1.

[0035] (2) Preparation of D-serine methyl ester L-DBTA di-salt:

[0036] Add 23.8g (0.20mol) of DL-serine methyl ester obtained in step (1) respectively, 180ml methanol, 2.1g (0.02mol) 4-formylpyridine in a reactor with stirring, heating, and a thermometer, while stirring Heat up to 35°C, add dropwise L-DBTA methanol solution [prepared from 35.8g (0.10mol) L-DBTA and 72ml methanol] within 3 hours, react at the same temperature for 3 hours after dropping, and cool the reaction solution to room temperature , filtered, and the filtrate was used mechanically. The crystals were rinsed with 30ml of methanol solvent for 3 times and then dried to obtain 47.1g of crystalline D-serine methyl ester L-DBTA disalt. The resolution yield was 79.2%, and the melting point was 168.5°C. Specific rotation

[0037] (3) Preparation of D-serine:

[0038] With the method of step (3) of Example 1, take 45.0g (0.075m...

Embodiment 3

[0040] (1) Preparation of DL-serine methyl ester is the same as in Example 1.

[0041] (2) Preparation of D-serine methyl ester L-DBTA di-salt:

[0042]Add respectively 23.8g (0.20mol) of DL-serine methyl ester obtained in step (1), 180ml methanol, 0.37g (0.002mol) 2-bromo-4-formylpyridine in a reactor with stirring, heating and a thermometer , heated up to 55°C while stirring, added dropwise L-DBTA methanol solution [prepared from 35.8g (0.10mol) L-DBTA and 140ml methanol] within 1 hour, and reacted at the same temperature for 1.5 hours after the drop was completed. The liquid was cooled to room temperature, filtered, and the filtrate was used mechanically. The crystals were washed with 30ml methanol solvent for 3 times and then dried to obtain 52.2g of crystalline D-serine methyl ester·L-DBTA di-salt. The resolution yield was 87.8%. : 168.1℃, specific rotation

[0043] (3) Preparation of D-serine:

[0044] With the method of step (3) of Example 1, take 50.0g (0.084mol) ...

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Abstract

The invention discloses a method for preparing D-serine by kinetic resolution. The method takes DL-serine as raw material and is implemented by esterifying DL-serine with methanol under catalysis of Amberlyst-15 ion exchange resin to obtain DL-serinemethylester, carrying out dynamic kinetic resolution on DL-serinemethylester and resolving agent L-DBTA under action of racemization catalyst to obtain dibasic DL-serinemethylester.L-DBTA, dissociating with hydrochloric acid, and hydrolyzing to obtain D-serine, the target product of the invention. Compared with the prior art, by using the racemization catalyst in the invention, the dynamic continuous conversion of dibasic L-serinemethylester.L-DBTA into dibasic DL-serinemethylester.L-DBTA can be realized with the theoretic conversion rate being approximate to 100%, thus greatly enhancing yield of resolution, reducing operation cost, stabilizing product quality and being suitable for industrialized production.

Description

technical field [0001] The invention relates to a method for preparing D-serine through kinetic resolution, in particular to a method for preparing D-serine through dynamic kinetic resolution with a racemization catalyst. Background technique [0002] D-serine is an important pharmaceutical intermediate, which can be used in the preparation of tissue culture medium by biochemical reagents, and used as amino acid nutritional medicine in medicine. Its structural formula is as follows: [0003] [0004] The existing literature "Amino Acids and Biological Resources" 2007, 29 (2): 40-41 reported "a new method for preparing D-serine with DL-serine as raw material" by Wu Liuyang, Department of Chemistry and Chemical Engineering, Southeast University, using DL-serine as Raw materials, the method for preparing D-serine through esterification, resolution and hydrolysis, that is, resolution of DL-serine methyl ester under the action of resolving agent L-2,3-dibenzoyltartaric acid (...

Claims

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Application Information

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IPC IPC(8): C07C229/22C07C227/34C07C227/30
Inventor 廖本仁安国成顾慧娟钱柯君
Owner SHANGHAI SHISI CHEM PROD
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