公开(公告)号：US3928331A

公开(公告)日：1975-12-23

申请号：US39287773

申请日：1973-08-30

Applicant: HOECHST AG

Inventor： BAUERSCHMIDT EBERHARD ,  BORMANN DIETER ,  WORM MANFRED

IPC: C07D501/04 ,  C07D20060101 ,  C07D501/16 ,  C07D501/18

CPC classification number: C07D499/00

Abstract: Process for the manufacture of 7-amino-3-cephem-4-carboxylic acids and the esters thereof of the formula I

in which A stands for hydrogen, alkyl, acyloxy, alkyloxy or hydroxy and R stands for hydrogen, optionally substituted linear or branched alkyl, cycloalkyl, aryl, aralkyl, aryloxyalkyl, alkoxyalkyl, acryloxyalkyl, aroylalkyl, or a heterocyclic radical and the salts thereof which comprises reacting 7-acylamino-3cephem-4-carboxylic acid esters of the general formula II

in which R'' stands for optionally substituted alkyl, aryl, aralkyl, aryloxyalkyl, alkoxyalkyl or a heterocyclic radical and R'''' has the meaning given for R but cannot stand for hydrogen and A is defined as above, in an inert solvent with a silylating agent in the presence of a base, converting the amido group activated by the silylation into the iminohalide by adding a halogenating agent, allowing it to react with an alcohol to yield the iminoether hydrohalide, hydrolyzing the iminoether hydrohalide and optionally splitting the 7-amino-3-cephem-4carboxylic acid ester of the general formula I to yield the free acid, the esters obtained being valuable intermediates.

Abstract translation: 制备7-氨基-3-头孢烯-4-羧酸的方法及其分子式Ⅰ的酯，其中A代表氢，烷基，酰氧基，烷氧基或羟基，R代表氢，任选取代的直链或支链 烷基，环烷基，芳基，芳烷基，芳氧基烷基，烷氧基烷基，丙烯酰氧基烷基，芳酰基烷基或杂环基及其盐，其包括使通式II的7-酰基氨基-3-头孢烯-4-羧酸酯与R' 对于任选取代的烷基，芳基，芳烷基，芳氧基烷基，烷氧基烷基或杂环基，R“具有R给出的含义，但不能代表氢，A如上所定义，在惰性溶剂中，在甲硅烷基化剂存在下， 碱，通过加入卤化剂将通过甲硅烷基活化的酰氨基转化成亚胺基卤化物，使其与醇反应得到亚氨基醚氢卤酸盐，水解亚氨基醚氢卤酸盐和任选的 制备通式I的7-氨基-3-头孢烯-4-羧酸酯，得到游离酸，得到的酯是有价值的中间体。