Synthetic method of amoxicillin production intermediate

Abstract

The invention relates to a synthesis method of an amoxicillin production intermediate, which comprises the following steps of: synthesizing D-p-hydroxyphenylglycine methyl ester by taking DL-p-hydroxyphenylglycine and methanol as raw materials and solid phosphoric acid as a catalyst; comprising the following five parts: preparation of a solid phosphoric acid catalyst, preparation of DL-p-hydroxyphenylglycine methyl ester, hydrolysis of the solid phosphoric acid catalyst, crystallization of D-p-hydroxyphenylglycine methyl ester and racemization of crystallization mother liquor. The solid phosphoric acid catalyst can be hydrolyzed into phosphoric acid after esterification is completed, phosphoric acid and DL-p-hydroxyphenylglycine methyl ester form phosphoric acid double salt, and phosphoric acid serves as an esterification catalyst for synthesis of DL-p-hydroxyphenylglycine methyl ester and also serves as a resolving agent of DL-p-hydroxyphenylglycine methyl ester. The synthesis and resolution of the DL-p-hydroxyphenylglycine methyl ester are carried out in the methanol aqueous solution, and the crystallization mother liquor is recycled, so that the generation of waste liquid is greatly reduced, and the method is a clean production process of the D-p-hydroxyphenylglycine methyl ester.

Description

technical field [0001] The invention relates to a method for synthesizing an intermediate for the production of amoxicillin, in particular to a method for synthesizing L-p-hydroxyphenylglycine methyl ester, which belongs to the field of new pharmaceutical and chemical materials. Background technique [0002] The chemical name of Amoxicillin is amoxicillin, which is the main species of second-generation penicillin and a broad-spectrum semi-synthetic antibiotic. It has a high-efficiency broad-spectrum antibacterial effect and minimal side effects. The World Health Organization (WHO) recommends it as the preferred β-lactam oral antibiotic. The synthetic methods of amoxicillin mainly include chemical synthesis and enzymatic synthesis. The enzymatic synthesis method uses D-p-hydroxyphenylglycine methyl ester (D-p-hydroxyphenylglycine methyl ester) and 6-aminopenicillin acid to directly synthesize amoxicillin under the catalysis of enzymes. It has the advantages of mild process c...

AI Technical Summary

Problems solved by technology

[0005] The prior art uses D-p-hydroxyphenylglycine as a raw material to esterify D-p-hydroxyphenylglycine methyl ester. Although the process is relatively simple, the raw material is expensive, the catalyst is difficult to separate, and the technical economy is not good.