PREPARATION OF (1-OXA- OR l-THIA-)3- CEPHEM DERIVATIVES

摘要

There is described a process for the preparation of carboxy-protected 7ß-amino-7a-methoxy-(l-oxa- or l-thia-)3-(l-substituted-lH-tetrazol-5-yl)thiomethyl-3- cephem-4-carboxylic acid. Said process comprises (a) reacting a carboxy- protected 7-amino-3-chloromethyl-(l-oxa- or 1-thia-) 3-cephem-4-carboxylate with an alkyl- or aryl-sulfenyl chloride; (b) reacting the corresponding 7-alkyl- or aryl-thioimino derivative with a l-(alkyl- o ?-hydroxyalkyl-)lH-tetrazol-5- ylthiol; and (c) reacting the corresponding 7-(alkyl- or aryl-)thioimino-3-(l- substituted-lH-tetrazol-5-yl)Momethyl- (1-oxa- or l-thia-)3-cephem with methanol in the presence of triphenylphosphine and aluminum chloride neutralized with a base. The reaction of the obtained carboxy-protected 7ß-amino- 7a-methoxy-(1-oxa- or 1 -thia-)3 -(1-substituted- 1H-tetrazol-5 -yl)thiomethyl-3 - cephem-4-carboxylic acid with activated 2-(cyanomethylthio)acetic or 2- (difiuoromethyl thio)acetic acid affords, after final removal of the protecting ester group, cefmetazole and fiomoxef, respectively. The 7-(alkyl- or aryl)thioimino-3- (1-substituted-1H-tetrazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem intermediates are new compounds.