Method for preparing 7-amido-3-vinyl cethalosporanic acid

Abstract

A method of preparing for 7-amido-3-ethylene cephalosporanic acid considers 7-phenylacetyl amino-3-chloromethyl cephalosporanic acid p-methoxybenzyl ester (GCLE) as a starting material and adopts the Wittig reaction. Ethylene is introduced on position 3 to obtain 7-phenylacetyl amino-3- ethylene-4- cephalosporanic acid p-methoxybenzyl ester, and a product GVNE is obtained. The GVNE is used to prepare for 7-amido-3-7 alkenyl cephalosporanic acid (7-AVCA). The present invention has the main technical characteristic that the triethyl phosphite with quite low price is used to replace triphenyl-phosphonium in the preparation of the GVNE to realize the purpose of introducing the ethylene on the position 3 of GCLE to prepare for the GVNE. The production method is simple; the cost of the main materials is low; the yield is high; the comprehensive benefit efficiency is high; the present invention is applicable to the large scale industrialized preparation of 7-AVCA.

Description

technical field [0001] The invention relates to a preparation method of a pharmaceutical intermediate, in particular to a synthesis method for producing 7-amino-3-vinyl cephalosporanic acid at low cost. Background technique [0002] 7-amino-3-vinyl cephalosporanic acid (7-AVCA) is an important raw material for the synthesis of the third generation cephalosporin cefixime. Cefixime (cefixime) is the third-generation oral cephalosporin, which was first developed and listed by Fujisawa Pharmaceutical Co., Ltd. in Japan. Its trade name was Cefspan. It was approved by the US FDA in 1987. It has surpassed cefuroxime axetil to become the oral cephalosporin with the largest market share. Now, this product is recorded in the pharmacopoeias of the United States, the United Kingdom, Japan and Europe, and has been widely clinically used in more than 80 countries. Cefixime is characterized by broad spectrum resistance, strong antibacterial effect, long duration of effective concentration...

AI Technical Summary

Problems solved by technology

[0004] As the market continues to change, the cost of the original process can no longer meet the needs of the market. Generally, there are disadvantages such as long cycle time, excessive waste, high cost of raw materials and low yield. The biggest problem is the current production of 7-AVCA. In the synthesis method, due to the synthesis of the key intermediate GVNE, triphenylphosphine needs to be used when vinyl is introduced into the 3-position of GCLE. On the one hand, triphenylphosphine is expensive, resulting in higher production costs; on the other hand, three The molecular weight of phenylphosphorus is relatively large, so that the amount of triphenylphosphorus used in production is also relatively large, which also greatly increases the production cost

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