Preparation method of 7-phenylacetamido-3-vinyl-4-p-methoxy benzyl ester cefotaximate

Abstract

The invention discloses a preparation method of 7-phenylacetamido-3-vinyl-4-p-methoxy benzyl ester cefotaximate and belongs to the Chemical medicine field. The preparation method comprises the following steps: carrying out quaternary phosphorization and vinyl reaction at the same time on 7-phenylacetamido-3-chloromethyl-4-p-methoxy benzyl ester cefotaximate (GCLE), sodium iodide, triphenylphosphine and formaldehyde solution in a mixed system of dichloromethane, acetone and water to obtain 7-phenylacetamido-3-vinyl-4-p-methoxy benzyl ester cefotaximate; and removing 7-amino and 4-carboxyl protecting group according to known methods to prepare cefixime and cefdinir nuclear parent 7-AVCA (7-amino-3-vinyl-4-cephalosporanic acid). The aqueous phase comprising sodium iodide and excessive formaldehyde can be repeatedly applied, so that the utilization ratio of sodium iodide is remarkably improved, the production cost is lowered, and the environmental pollution caused by formaldehyde is reduced. The preparation method disclosed by the invention is low in production cost, simple in operating method and suitable for industrialized production and the raw materials are easily available in the preparation process.

Description

technical field [0001] The invention relates to a preparation method of a pharmaceutical intermediate 7-phenylacetamido-3-vinyl-4-cephem acid p-methoxybenzyl ester, which belongs to the field of medicine and chemical industry. Background technique [0002] 7-Amino-3-vinyl-4-cephemic acid (7-AVCA) is the mother nucleus for the production of cefixime and cefdinir. The preparation methods reported in the literature include: 1. Using penicillin G potassium salt as a starting material, it is prepared through a series of reactions such as ring opening and ring expansion; ), treated with organic silicon reagents, and prepared by reacting with formaldehyde under strong alkali and anhydrous conditions; As a raw material, it can be prepared by removing 4-carboxyl and 7-amino protecting groups through quaternary phosphine and vinylation. Although the raw materials of the first preparation route are easy to obtain, the reaction steps are long and the yield is low, so it is difficult t...

AI Technical Summary

Problems solved by technology

Although the raw materials of the first preparation route are easy to obtain, the reaction steps are long, the yield is low, and it is difficult to realize industrialization

The second route requires expensive organosilicon reagents such as hexamethylsilyldisilazane and iodotrimethylsilane and strong organic bases. The reaction process needs to be completed under absolutely anhydrous conditions. The production conditions are harsh, difficult to control, and also difficult for the industry. change

The improved method of quaternary phosphine and vinylation is also carried out step by step, which also cannot solve the environmental pollution problems caused by sodium iodide recovery and reuse and excessive formaldehyde solution

[0005] In summary, in the known process of preparing 7-phenylacetamido-3-vinyl-4-cephenoic acid p-methoxybenzyl ester from GCLE, it is difficult to recover expensive sodium iodide, which is not conducive to recycling , resulting in high production costs; excess formaldehyde solution cannot be recovered, causing production environmental pollution