A kind of synthetic method of amoxicillin production intermediate

Abstract

The present invention relates to a kind of synthesis method of amoxicillin production intermediate, use DL-p-hydroxyphenylglycine and methanol as raw materials, and use solid phosphoric acid as catalyst to synthesize D-p-hydroxyphenylglycine methyl ester, including preparation of solid phosphoric acid catalyst, DL-p-hydroxyphenylglycine Preparation of p-hydroxyphenylglycine methyl ester, hydrolysis of solid phosphoric acid catalyst, crystallization of D-p-hydroxyphenylglycine methyl ester and racemization of crystallization mother liquor in 5 parts. In the present invention, the solid phosphoric acid catalyst can be hydrolyzed into phosphoric acid after the esterification is completed, and forms a phosphoric acid double salt with DL-p-hydroxyphenylglycine methyl ester. ‑Resolving agent for methyl p-hydroxyphenylglycine. In the present invention, the synthesis and resolution of DL-p-hydroxyphenylglycine methyl ester is carried out in methanol aqueous solution, and the crystallization mother liquor is recycled, which greatly reduces the generation of waste liquid, and is a clean production process of 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.