Novel method for preparing cefroxadine parent nucleus 7-AMOCA

Abstract

The invention discloses a novel method for preparing a cefroxadine parent nucleus 7-AMOCA. The method comprises the following steps: (1) preparing a methide: adding 3-hydroxycephalosporin, N,N-dimethylformamide and potassium carbonate in the stirring process, heating the obtained mixture, adding dimethyl carbonate, performing stirring until a reaction is finished, cooling the reacted mixture to room temperature, adding water and dichloromethane, performing stirring until uniformity, standing for layering, and drying and concentrating the obtained mixture to obtain the methide; and (2) preparing the cefroxadine parent nucleus: adding dichloromethane, dibromotriphenylphosphine and 2,6-dimethylpyridine in a nitrogen introducing state, cooling the obtained mixture, adding the methide and m-cresol, performing stirring until a reaction is finished, adding water, performing stirring until uniformity, standing for layering, adjusting the pH value of the obtained water layer to crystallize thewater layer, and drying obtained crystals to obtain the white cefroxadine parent nucleus 7-AMOCA. The method has the advantages of easily available raw materials, simplification of a three-step reaction into a two-step reaction, avoiding of the highly-toxic reagent dimethyl sulfate from being used in the preparation of the cefroxadine parent nucleus, simplicity in operation, and improved yield.

Description

technical field [0001] The invention relates to the technical field of preparation of cephalosporin intermediates, in particular to a new method for preparing cefoxadin core 7-AMOCA. Background technique [0002] As an oral cephalosporin, cefoxadin has broad-spectrum antibacterial activity and has bactericidal effects on Staphylococcus, Escherichia coli, Influenza Bacillus, Klebsiella, etc. Infections in organs and other parts are also commonly used for otitis media. 7-AMOCA is the key mother nucleus for the synthesis of cefoxadin, and its chemical name is (6R,7R)-7-amino-3-methoxy-8-oxo-5-thia-1-azabicyclo[4.2. 0] Oct-2-ene-2-carboxylic acid, molecular structural formula is: [0003] [0004] There are mainly 2 synthetic technical routes of the existing cefoxadin nucleus 7-AMOCA. Route 1 is obtained through methylation and deprotection reaction with 3-OH cephem compound as the starting reaction material. The reaction route is as follows : [0005] [0006] Route 2...

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Problems solved by technology

Inhalation can lead to necrosis of tracheal and bronchial epithelial cells, puncture leading to mediastinal or subcutaneous emphysema; serious bodily harm to workshop workers

[0009] The diazomethane used in the above synthesis method of route 2 belongs to explosives, and it is very easy to explode when it is heated, exposed to open flame, or subjected to vibration and friction; and inhalation has a strong stimulating effect on the respiratory tract and inhibits the central nervous system. effect, can cause dyspnea, chest pain; therefore not suitable for industrial production

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