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Preparation method of 2-chlorophenylglycine

A technology of o-chlorophenylglycine and o-chlorobenzaldehyde is applied in the preparation of organic compounds, chemical instruments and methods, preparation of cyanide reaction, etc., and can solve the problems of difficulty in recycling ammonia water, high cost of recovering methanol, and high equipment requirements, To achieve the effect of reducing post-processing pressure, reducing production costs, and environmental protection in the production process

Inactive Publication Date: 2019-05-07
九江中星医药化工有限公司
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  • Abstract
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Problems solved by technology

[0005] The method of preparing o-chlorophenylglycine in this patent has the problems of high cost of methanol recovery, difficulty in recycling ammonia water and high equipment requirements, and there is a certain pollution to the environment

Method used

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  • Preparation method of 2-chlorophenylglycine

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[0029] The invention provides a kind of preparation method of o-chlorophenylglycine, comprising the following steps:

[0030] (1) water, cyanide salt solution and o-chlorobenzaldehyde are mixed, carry out nucleophilic addition reaction under the effect of phase-transfer catalyst, obtain the nucleophilic addition reaction liquid comprising 2-chloro-α-hydroxyphenylacetonitrile;

[0031] (2) the nucleophilic addition reaction solution obtained in step (1) is mixed with carbonate to carry out the Bucherer-Berger reaction, to obtain the Bucherer-Berger reaction solution comprising o-chlorophenylhydantoin;

[0032] (3) The Bucherer-Berg reaction solution obtained in step (2) is subjected to alkali hydrolysis, decolorization and acidification in sequence to obtain o-chlorophenylglycine.

[0033] The concrete reaction process of preparation method provided by the invention is as shown in formula I:

[0034]

[0035] The present invention mixes water, cyanide salt solution and o-ch...

Embodiment 1

[0046] Water (200 mL), tetrabutylammonium bromide (5.7 g) and 30% sodium cyanide solution (70.0 g) were added to a 500 mL three-necked flask, and the system was stirred at room temperature for 30 min. O-chlorobenzaldehyde (50.0 g) was added to the system. After the addition was complete, the system was slowly warmed up to 35° C. for 4 hours. After the reaction was completed, ammonium bicarbonate (79.0 g) was added to the system. After the addition was complete, the system continued to react at 55° C. for 4 h.

[0047] After the reaction is finished, add 30% liquid caustic soda to the system to adjust the pH value of the system to ≥12. Then the reaction solution was transferred into a self-boosting high-pressure reactor, the temperature of the system was raised to 135° C., the pressure was 0.3 MPa, and the reaction was carried out for 5 hours.

[0048] After the reaction, the temperature of the system was lowered to 70° C., activated carbon (1 g) was added, and the mixture was...

Embodiment 2

[0050] Water (200 mL), trimethylbenzyl ammonium chloride (5.0 g) and 30% sodium cyanide solution (70.0 g) were added to a 500 mL three-necked flask, and the system was stirred at room temperature for 30 min. O-chlorobenzaldehyde (50.0 g) was added to the system. After the addition was complete, the system was slowly warmed up to 30° C. for 6 h. After the reaction was completed, ammonium bicarbonate (79.0 g) was added to the system. After the addition was complete, the system continued to react at 60° C. for 6 h.

[0051] After the reaction is finished, add 30% liquid caustic soda to the system to adjust the pH value of the system to ≥12. Then the reaction solution was transferred into a self-boosting high-pressure reactor, the temperature of the system was raised to 135° C., the pressure was 0.3 MPa, and the reaction was carried out for 5 hours.

[0052] After the reaction, the temperature of the system was lowered to 70° C., activated carbon (1 g) was added, and the mixture ...

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Abstract

The invention provides a preparation method of 2-chlorophenylglycine. The preparation method comprises the following steps: mixing water, a cyanide solution and 2-chlorobenzaldehyde, and carrying outa nucleophilic addition reaction under the action of a phase transfer catalyst to obtain a nucleophilic addition reaction solution containing 2-chloro-alpha-hydroxyphenylacetonitrile; then mixing thenucleophilic addition reaction solution with a carbonate to carry out a Bucherer-Bergs reaction to obtain a Bucherer-Bergs reaction solution containing 2-chlorophenylhydantoin; and then sequentially carrying out alkali hydrolyzing, decoloring and acidifying on the Bucherer-Bergs reaction solution to obtain the 2-chlorophenylglycine. In the preparation method provided by the invention, organic solvents and ammonia water are not used, so that generation of chemical oxygen demand (COD) and ammonia nitrogen in production wastewater is reduced, post-treatment load of the wastewater is reduced, theproduction process is more environmentally friendly, and meanwhile, production cost is reduced. In addition, the 2-chlorophenylglycine is prepared by adopting a method for stepwise synthesizing the 2-chlorophenylhydantoin, and the problem that the color and yield of the product are influenced due to the fact that colored impurities are easily generated in an existing ''one-pot boiling'' method issolved.

Description

technical field [0001] The invention relates to the technical field of pharmaceutical intermediates, in particular to a preparation method of o-chlorophenylglycine. Background technique [0002] O-chlorophenylglycine is a kind of important intermediate used for preventing and treating heart, brain and other arterial circulation disorder medicine clopidogrel (chopidogrel) caused by high platelet aggregation. The main method of synthesizing o-chlorophenylglycine is to use o-chlorobenzaldehyde as the main raw material to obtain the target product through cyanation, hydrolysis, decolorization, and neutralization. [0003] Chinese patent CN 101058547 describes that in the presence of methanol, water and bicarbonate, add cyanide salt solution and ammonia water, and then add o-chlorobenzaldehyde, "one pot cooking" to prepare o-chlorophenylhydantoin, and then undergo alkali hydrolysis and decolorization , neutralization and other processes to prepare o-chlorophenylglycine. Its ind...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C227/18C07C229/36C07D233/76
Inventor 骆建轻周以鸿赖立冬程龙进何文秀
Owner 九江中星医药化工有限公司
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