Method for preparing 7-phenylacetylamino-3-hydroxyl-3-cyclo-4-p-nitrobenzyl cephalosporin carboxylate

Abstract

The invention belongs to the field of preparation methods for compounds and particularly relates to a method for preparing 7-phenylacetylamino-3-hydroxyl-3-cyclo-4-p-nitrobenzyl cephalosporin carboxylate. The 7-phenylacetylamino-3-hydroxyl-3-cyclo-4-p-nitrobenzyl cephalosporin carboxylate is prepared from thiazoline enol ester, which serves as a raw material, by a one-pot method through acylation, ene-amination, bromization and cyclization. According to the method, through one-pot method continuous reactions, the operation is simple, the total reaction time is shortened, and the energy consumption is greatly lowered; and the reaction process is carried out at normal temperature or under the condition of being close to room temperature, the reaction conditions are mild, the reaction time is relatively short, the raw materials used are readily available, the cost is low, the pollution is light, the total yield reaches 82.5% or more, the purity can reach 98.0% or more, and the quality of the product is relatively good, so that the method is applicable to industrial production.

Description

technical field [0001] The invention belongs to the field of compound preparation methods, and in particular relates to a preparation method of 7-phenylacetamido-3-hydroxyl-3-cephalosporin-4-carboxylic acid p-nitrobenzyl ester. Background technique [0002] 7-Amino-3-chloro-3-cephalosporin-4-carboxylic acid is the key mother nucleus for the preparation of antibiotic cefaclor, referred to as 7-ACCA, and 7-phenylacetamido-3-hydroxyl-3-cephalosporin-4- Carboxylic acid p-nitrobenzyl ester is a key intermediate for the preparation of 7-amino-3-chloro-3-ceph-4-carboxylic acid. But the technology of my country's production 7-amino-3-chloro-3-cephalosporin-4-carboxylic acid is still immature at present, and the preparation cost of each intermediate is higher, and yield is low, pollutes serious simultaneously, makes the production of multiple cephalosporins Production is constrained. [0003] In the preparation method described in the patent whose application publication number is C...

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Problems solved by technology

But the technology of my country's production 7-amino-3-chloro-3-cephalosporin-4-carboxylic acid is still immature at present, and the preparation cost of each intermediate is higher, and yield is low, pollutes serious simultaneously, makes the production of multiple cephalosporins Production is constrained

[0003] In the preparation method described in the patent whose application publication number is CN103694257A, the raw materials used are highly toxic, seriously pollute the environment, and the price is high, so that the cost is also high

[0004] In the preparation method described in the patent whose application publication number is CN103387584A, the raw materials used are highly toxic, the environment is seriously polluted, and the price is high, so that the cost is also high

[0005] In the patent application No. US4064343, the raw materials used are highly toxic, the yield is low, and the cost is high

[0006] Although the patent application No. US4079181 also adopts a one-pot method to synthesize 7-phenylacetamido-3-hydroxyl-3-cephalosporin-4-carboxylic acid p-nitrobenzyl ester from thiazoline enol ester , but its yield is low, and the raw materials used are easy to cause pollution to the environment

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