The Study Of Synthetic Process Of Intermediates Of Oxycephem Antibiotics

The structure of oxacephem antibiotics is similar to cephalosporins,its ant-i bacterial spectrum is similar to the other third generation cephalosporins,suc h as latamoxef and flomoxef.These drugs have strong function and wide antimi crobial spectrum,it was been used for respiratory infection,urinary tract infection,gynecologic infection,surgical infection and obstetrics infection,et al,it is very broad of the application prospect and the market potential.(2R,6R,7R)-7-(2-methylbenzoylamino)-3-methylene-8-oxo-5-oxa-1-azabic-yc l-o [4.2.0] octane-2-carboxylic acid benzhydryl ester is an important intermediate for the synthesis of oxyceenes such as latamoxef and flomoxef.This pap-er focuses on the synthesis of the intermediate of oxo cephalosporin,which is an industrial and economical synthesis method.The yield is stable,the ra-w m aterial is cheap and easy to be obtained,and it has a good prospect of industr ial application.The specific process of each step is as follows:(1)Chloroallyl compound is synthesized by using allyl compound as [1R-[1alpha,5alpha,6(R)]]-alpha-(1-methylethenyl)-3-(2-methylphenyl)-7-oxo-4-Oxa-2,6-d-i a-zabicyclo[3.2.0]hept-2-ene-6-acetic acid diphenylmethyl ester through chlorine addition,dehydrochlorination and used solvent of dichloromethane,the yield of this step is 78%.(2)Hydroxylated allyl compound is synthesized by using non proton p-methyl-benzenesulfonic acid as catalyst,with cuprous oxide and water,with DMSO as solvent,the yield of this step is 82.5%.(3)The target molecules of(2R,6R,7R)-7-(2-methylbenzoylamino)-3-me-thylene-8-oxo-5-oxa-1-azabicyc-lo [4.2.0] octane-2-carboxylic acid benzhydryl es-ter is synthesized of the cyclization reaction with dichloromethane,with using boron trifluoride etherate as catalyst,the yield of this step is 90%.The tot-al yield is have 56.2% of this route.