Preparation method of D-para hydroxybenzene glycine methyl ester

A technology for p-hydroxyphenylglycine methyl ester and p-hydroxyphenylglycine, which is applied in the field of enzymatic synthesis of D-p-hydroxyphenylglycine methyl ester of amoxicillin, can solve the problems of cumbersome steps, unsatisfactory, difficult to control, and the like, To achieve the effect of simple process steps, simplification of operation steps, and reduction of workshops

Inactive Publication Date: 2013-05-22
NORTH CHINA PHARM GRP SEMISYNTECH CO LTD
View PDF3 Cites 12 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although this method avoids the corrosion of equipment to a certain extent and has the advantages of environmental protection, its

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Preparation method of D-para hydroxybenzene glycine methyl ester

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0018] Preparation of hydrogen chloride gas: Take 49g of ammonium chloride and add it to the gas generating device, add 90g of concentrated sulfuric acid dropwise, and collect 13.9g of hydrogen chloride gas for future use.

[0019] Preparation of D-p-hydroxyphenylglycine methyl ester (as figure 1 shown):

[0020] a. Passing pre-prepared hydrogen chloride gas into methanol to obtain a methanolic hydrogen chloride solution, wherein the mass-volume concentration of hydrogen chloride is 7%.

[0021] b. Add D-p-hydroxyphenylglycine to the hydrogen chloride methanol solution, wherein the molar ratio of D-p-hydroxyphenylglycine to hydrogen chloride is 2:1, then heat it in a water bath to 65°C, and reflux for 2 hours to obtain D-p-hydroxyphenylglycine Phenylglycine methyl ester methanol solution, the reaction conversion rate is 96.8%.

[0022] c. Place the methanol solution of D-p-hydroxyphenylglycine methyl ester above under the conditions of 40°C and vacuum degree of -0.08MPa, dis...

Embodiment 2

[0024] Prepare hydrogen chloride gas according to a conventional method: take 40 g of ammonium chloride and add it to the gas generator, add 73 g of concentrated sulfuric acid dropwise, and collect 15.27 g of hydrogen chloride gas for future use.

[0025] Preparation of D-p-hydroxyphenylglycine methyl ester:

[0026] a. Passing pre-prepared hydrogen chloride gas into methanol to obtain a methanolic hydrogen chloride solution, wherein the mass-volume concentration of hydrogen chloride is 14%.

[0027] b. Add D-p-hydroxyphenylglycine to the above hydrogen chloride methanol solution, wherein the molar ratio of D-p-hydroxyphenylglycine to hydrogen chloride is 3.5:1, then heat it in a water bath to 80°C, and reflux for 4 hours to obtain D-p-hydroxyphenylglycine Phenylglycine methyl ester methanol solution, the reaction conversion rate is 97.6%.

[0028] c. Place the above D-hydroxyphenylglycine methyl ester methanol solution at 70°C and a vacuum of -0.09MPa, distill under reduced ...

Embodiment 3

[0030] Preparation of hydrogen chloride gas: Measure 500 mL of concentrated hydrochloric acid, heat, collect and obtain 8.2 g of hydrogen chloride gas for future use.

[0031] Preparation of D-p-hydroxyphenylglycine methyl ester:

[0032] a. Passing pre-prepared hydrogen chloride gas into methanol to obtain a methanolic hydrogen chloride solution, wherein the mass-volume concentration of hydrogen chloride is 10%.

[0033] b. Add D-p-hydroxyphenylglycine to the methanolic hydrogen chloride solution, wherein the molar ratio of D-p-hydroxyphenylglycine to hydrogen chloride is 2.5:1, then heat it in a water bath to 75°C, and reflux for 3 hours to obtain D-p-hydroxyl Phenylglycine methyl ester methanol solution, the reaction conversion rate is 98.5%.

[0034] c. Place the methanol solution of D-p-hydroxyphenylglycine methyl ester above under the conditions of 50°C and vacuum degree of -0.085MPa, distill under reduced pressure until no distillate is distilled, and add water until t...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention provides a preparation method of D-para hydroxybenzene glycine methyl ester. The method comprises the following steps of: firstly, preparing a hydrochloric acid methanol solution; adding D-para hydroxybenzene glycine into the hydrochloric acid methanol solution to perform reflux reaction for 2-4 hours at 65-80 DEG C; performing pressure reduction distillation and removing methanol; and adding water to obtain a D-para hydroxybenzene glycine methyl ester aqueous solution. Based on that, the invention also provides anenzymatic synthesis method of amoxicillin. The method comprises the following steps of: adding 6-APA and immobilized penicillin acylase into the D-para hydroxybenzene glycine methyl ester aqueous solution to react for 1-8 hours at 10-30 DEG C; regulating the pH value of a reaction liquid to 0.8-1.0 by using hydrochloric acid or sulfuric acid aqueous solution; regulating the pH value to 4.5-6.0 by using ammonia water or sodium hydroxide aqueous solution to crystallize for 1-5 hours at 0-30 DEG C; separating solid from liquid; collecting a solid; and washing and drying to obtain amoxicillin. The method is simple in steps, and low in cost; and the obtained -para hydroxybenzene glycine methyl ester is high in yield and less in impurities and can be directly applied to anenzymatic synthesis of amoxicillin.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical engineering, and in particular relates to a method for enzymatically synthesizing D-p-hydroxyphenylglycine methyl ester from amoxicillin. Background technique [0002] Amoxicillin is the most commonly used β-lactam antibiotic. There are usually two methods of synthesizing amoxicillin: one is chemical synthesis, and the other is enzymatic synthesis (referred to as enzymatic method). The enzymatic method uses the catalysis of immobilized penicillin acylase to generate amoxicillin from the reaction of the mother nucleus 6-aminopenicillanic acid (6-APA) and the side chain D-p-hydroxyphenylglycine methyl ester. Compared with the chemical synthesis method, the enzymatic method does not require the use of organic solvents, the reaction conditions are mild, the energy consumption is low, the operation is convenient, and the product quality is better. [0003] At present, the raw material D-p-hydr...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): C07C229/36C07C227/18C12P37/04
Inventor 左丽华刘慧勤严正人吴浩尹松涛
Owner NORTH CHINA PHARM GRP SEMISYNTECH CO LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap