Method of preparing o-chlorophenyl glycine

A technology of o-chlorophenylglycine and o-chlorobenzaldehyde, applied in the field of medicine and chemical industry, can solve the problems of high safety cost, heavy environmental pollution, long reaction time, etc., and achieve the effects of guaranteed quality, short production cycle and simple operation

Active Publication Date: 2007-10-24
ZHEJIANG APELOA JIAYUAN PHARMA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Aiming at the defects of the existing preparation method of o-chlorophenylglycine, such as long reaction time, low yield, high safety cost and heavy environmental pollution, the pr

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Get 42ml of methanol and 23.5g of ammonium bicarbonate and put it into a three-necked flask, then add 108g of 30% sodium cyanide solution, stir for 10 minutes after adding, add 67ml of ammonia water and pass through a constant temperature magnetic stirrer (manufactured by Yingyu Yuhua Instrument Factory, Gongyi City) Stir for 10 minutes, then add 25g of o-chlorobenzaldehyde, stir for 20 minutes, heat up to 30°C for 5 hours, then heat up to 80°C, react for 4 hours, concentrate at 70°C under normal pressure after the reaction, distill 60ml of distillate Add 83ml of drinking water to the reaction bottle, and add 30% NaOH aqueous solution to adjust the pH to ≥12, then heat up to catch ammonia, the temperature gradually rises to 90°C to catch ammonia, the time to catch ammonia is about 2 hours, and the ammonia gas is absorbed by water.

[0028] After catching ammonia, put the above reaction liquid into a high-pressure reactor, adjust the pH to 12 with 30% NaOH aqueous solutio...

Embodiment 2

[0031] Take 42ml of methanol and 23.5g of ammonium bicarbonate and put them into a three-necked flask, then add 108g of 30% sodium cyanide solution, stir for 15 minutes after the addition, add 67ml of ammonia water and stir for 15 minutes, then add 25g of o-chlorobenzaldehyde, and stir for 30 minutes. Raise the temperature to 40°C for 4 hours, then raise the temperature to 60°C, and react for 6 hours. After the reaction, concentrate at 90°C under normal pressure, distill off 90ml of distillate, add 83ml of drinking water to the reaction bottle, and add 30% KOH aqueous solution to adjust the pH After ≥12, the temperature is raised to catch ammonia, and the temperature gradually rises to 100°C. The ammonia catchment time is about 1.5 hours, and the ammonia gas is absorbed by water.

[0032] Put the above reaction solution into a high-pressure reactor, adjust the pH to 12 with 30% KOH aqueous solution, then raise the temperature to 130°C, the pressure is 0.3MPa, hydrolyze at a con...

Embodiment 3

[0035] Put 42ml of methanol and 23.5g of ammonium bicarbonate into a three-necked flask, then add 108g of 30% sodium cyanide solution, stir for 12 minutes after the addition, add 67ml of ammonia water and stir for 12 minutes, then add 25g of o-chlorobenzaldehyde, and stir for 25 minutes. Raise the temperature to 60°C for 5 hours, then raise the temperature to 80°C, react for 4 hours, concentrate at 80°C under normal pressure after the reaction, distill 70ml of distillate, add 83ml of drinking water to the reaction bottle, and add 30% NaOH aqueous solution to adjust After PH ≥ 12, the temperature is raised to catch ammonia, and the temperature gradually rises to 120°C to catch ammonia. The ammonia catchment time is about 0.5 hours, and the ammonia gas is absorbed by water.

[0036] Put the above reaction solution into a high-pressure reactor, use 30% NaOH aqueous solution to adjust the pH to ≥ 12, then raise the temperature to 170°C, the pressure is 0.6MPa, and hydrolyze at a co...

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PUM

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Abstract

The invention discloses a preparing method of o-chlorobenzene glycine as chloropygray intermediate, which comprises the following steps: A. cyaniding; B. proceeding basic hydrolysis; decoloring; C. neutralizing; crystallizing; D. sucking; drying. The invention is fit for large scale of industrial manufacturing, which avoids toxic hydrocyanic acid from producing.

Description

technical field [0001] The invention relates to a preparation method of a pharmaceutical intermediate, in particular to a preparation method of a clopidogrel intermediate o-chlorophenylglycine, and belongs to the field of pharmaceutical chemical industry. Background technique [0002] Clopidogrel (clopidogrel), its chemical name is (+)-2-(2-chlorophenyl)-2-(4,5,6,7-tetrahydrothiophene[3,2-c]pyridin-5 ) methyl acetate, clopidogrel is an effective drug for the treatment of atherosclerosis, cerebrovascular disease and stroke, inhibits platelet activation by inhibiting the ADP pathway, thereby inhibiting platelet aggregation. O-chlorophenylglycine is an important intermediate for the synthesis of clopidogrel, and its preparation method has been reported in the literature. The existing method for synthesizing o-chlorophenylglycine is to use o-chlorobenzaldehyde as the main raw material, which is obtained by cyanidation, hydrolysis, and neutralization. target product. [0003] M...

Claims

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Application Information

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IPC IPC(8): C07C229/36C07C227/12
Inventor 申屠有德李仲新胡佳鹏李志红
Owner ZHEJIANG APELOA JIAYUAN PHARMA
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