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Preparation method of D-phenylglycine methyl ester hydrochloride/D-dihydrophenylglycine methyl ester hydrochloride

A technology of dihydrophenylglycine methyl ester and dihydrophenylglycine, which is applied in the field of preparation of D-phenylglycine methyl ester hydrochloride/D-dihydrophenylglycine methyl ester hydrochloride, can solve the problems affecting production , low product quality and other issues, to achieve the effect of benefiting industrial production, high purity and increasing profits

Active Publication Date: 2019-08-16
NORTH CHINA PHARMA COMPANY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The purpose of the present invention is to provide a kind of preparation method of D-phenylglycine methyl ester hydrochloride / D-dihydrophenylglycine methyl ester hydrochloride, to solve the low product quality when existing method mother liquor applies mechanically, influence follow-up production question

Method used

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  • Preparation method of D-phenylglycine methyl ester hydrochloride/D-dihydrophenylglycine methyl ester hydrochloride
  • Preparation method of D-phenylglycine methyl ester hydrochloride/D-dihydrophenylglycine methyl ester hydrochloride

Examples

Experimental program
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Effect test

Embodiment 1

[0028] in 2M 3 In the reaction tank, add 1200L of methanol, and add 400Kg of D-phenylglycine while stirring. After stirring evenly, add 460Kg of thionyl chloride, and control the temperature below 50°C. 4h, the reaction ended. Then carry out vacuum distillation, and the vacuum degree in the reactor is maintained at 0.03MPa. After the mass content of methanol in the solution in the reaction tank reaches 15%, stop the vacuum distillation, cool down and crystallize, drop to 0°C, stir for 30-60min, then centrifuge, and vacuum-dry at 50°C for 8h to obtain D-phenylglycine methyl ester salt Salt 480Kg.

[0029] The volume of the mother liquor was 250L, and then vacuum concentrated to 62.5L, cooled to 0°C, and then centrifuged to obtain a yellow recovered product; the recovered product was rinsed with 4Kg of methyl acetate, and vacuum-dried at 50-60°C to obtain a white recovered product of 26.0Kg ( The content of D-phenylglycine is 31.0%); the recovered product is applied mechanica...

Embodiment 2

[0031] in 2M 3 Add 1223.4L of methanol to the reaction tank, add 400Kg of D-phenylglycine and 26Kg of recovered product (containing 31.0% phenylglycine) under stirring, after stirring evenly, add 469Kg of thionyl chloride, control the temperature below 50°C, and complete the dropwise addition Afterwards, the temperature in the reactor was maintained at 59° C., and the reaction was completed by reflux for 4 hours. Then carry out vacuum distillation, and the vacuum degree in the reactor is maintained at 0.03MPa. After the mass content of methanol in the solution in the reaction tank reaches 15%, stop the vacuum distillation, cool down and crystallize, drop to 0°C, stir for 30-60min, then centrifuge, and vacuum-dry at 50°C for 8h to obtain D-phenylglycine methyl ester salt Salt 508Kg (mol yield: 95.49%), purity 99.6%, color grade and turbidity both 1#, light transmission 98.4%, see Table 1 for details.

[0032] The volume of the mother liquor is 250L, then vacuum concentrated t...

Embodiment 3

[0034] in 2M 3 Add 1223.4L of methanol to the reaction tank, add 400Kg of D-phenylglycine and 26Kg of recovered product (containing 31.4% of phenylglycine) under stirring, after stirring evenly, add 469Kg of thionyl chloride, control the temperature below 50°C, and complete the dropwise addition Afterwards, the temperature in the reactor was maintained at 60° C., refluxed for 4 hours, and the reaction was completed. Then carry out vacuum distillation, and the vacuum degree in the reactor is maintained at 0.03MPa. After the mass content of methanol in the solution in the reaction tank reaches 16%, stop the vacuum distillation, cool down and crystallize, drop to 0°C, stir for 30-60min, then centrifuge, and vacuum-dry at 50°C for 8h to obtain D-phenylglycine methyl ester salt Salt 509Kg (mol yield: 95.68%), purity 99.7%, color grade and turbidity both 1#, light transmission 98.5%, see Table 1 for details.

[0035] The volume of the mother liquor is 250L, then concentrated in va...

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Abstract

The invention provides a preparation method of D-phenylglycine methyl ester hydrochloride / D-dihydrophenylglycine methyl ester hydrochloride. The method comprises the following steps: (a) adding D-phenylglycine or D-dihydrophenylglycine and methanol into a reaction tank according to a ratio of 1 g:3-5 mL, performing uniform stirring, and slowly adding thionyl chloride; (b) after the thionyl chloride is added, performing a reflux reaction; (c) performing vacuum distillation, performing cooling crystallization, performing centrifugation, and performing drying to obtain a white product; (d) recovering the reaction mother liquid, performing vacuum concentration on the mother liquid, performing cooling crystallization, and performing centrifugation to obtain a yellow recovered product; (e) washing the yellow recovered product by using an organic reagent, and performing vacuum drying to obtain a white recovered product; and (f) recycling the white recovered product in the reaction tank, and preparing latter batch products according to operation of steps (a) to (c). The method provided by the invention proposes a novel way of recycling the mother liquid, and the product has more stable quality, high purity, and excellent color grade and turbidity.

Description

technical field [0001] The invention belongs to the technical field of medicine and chemical industry, and in particular relates to a preparation method of D-phenylglycine methyl ester hydrochloride / D-dihydrophenylglycine methyl ester hydrochloride. Background technique [0002] D-phenylglycine methyl ester hydrochloride, D-dihydrophenylglycine methyl ester hydrochloride is white powder or crystal, D-phenylglycine methyl ester hydrochloride is the side of enzymatic ampicillin, cephalexin, cefaclor Chain, D-dihydrophenylglycine methyl ester hydrochloride is the side chain of enzymatic cephradine. [0003] The synthesis method of D-phenylglycine methyl ester hydrochloride mentioned in "Synthesis of Cefaclor Active Side Chain Phenylglycine Methyl Ester Hydrochloride" published by Zheng Guixian (Zhejiang Angli Pharmaceutical Co., Ltd.) in 2014 is to use dichloro Thionization method, which is to slowly add thionyl chloride to methanol solution below 35°C to generate methyl sulfo...

Claims

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Application Information

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IPC IPC(8): C07C227/18C07C229/36C07C229/32
CPCC07C227/18C07C229/36C07B2200/07C07C2601/16C07C229/32
Inventor 张军立孙华刘倩张致一赵庆年赵华李珠徐颖
Owner NORTH CHINA PHARMA COMPANY
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