Patent ID: 6313289
Filing Date: 2001-11-06
Classification: C07D

Abstract:
A process for the production of cefixime of formula ##STR13##comprisinga. reacting a 7-amino-3-vinyl-3-cephem-4-carboxylic acid of formula ##STR14##wherein R.sub.5 denotes hydrogen or a leaving group, R.sub.6 denotes hydrogen and R.sub.7 denotes hydrogen, alkyl, cycloalkyl, alkylaryl, aryl, arylalkyl or a silyl protecting group; with a 2-(aminothiazol-4-yl)-2-carboxymethoxyimino)acetic acid ester of formula ##STR15##in free form or in form of a salt or a solvate,wherein R.sub.9 denotes alkyl, cycloalkyl, alkylaryl, aryl or arylalkyl, R.sub.10 denotes hydrogen and R.sub.11 denotes hydrogen, a silyl protecting group or (C.sub.1-24) carboxylic acid acyl group, to give a 7-[2-(aminothiazol-4-yl)-2-(carboxy-methoxyimino)acetamido]-3-vinyl-3-ceph em-4-carboxylic acid of formula ##STR16##wherein R.sub.7, R.sub.9, R.sub.10 and R.sub.11 are as defined above,b. reacting a 7-[2-(aminothiazol-4-yl)-2-(carboxymethoxyimino)-acetamido]-3-vinyl-3-ceph em-4-carboxylic acid of formula IA, wherein R.sub.7 is H and R.sub.9, R.sub.10 and R.sub.11 are as defined above, with an amine of formula ##STR17##wherein R.sub.1, R.sub.2 and R.sub.3 independently of each other denote hydrogen, alkyl, cycloalkyl, alkylaryl, aryl or aralkyl,to give a crystalline salt of a compound of formula IA, wherein R.sub.7 is H and R.sub.9, R.sub.10 and R.sub.11 are as defined above with an amine of formula VI, wherein R.sub.1, R.sub.2 and R.sub.3 are as defined above,c. reacting said crystalline salt of a compound of formula IA, wherein R.sub.7 is H and R.sub.9, R.sub.10 and R.sub.11 are as defined above with an amine of formula VI, wherein R.sub.1, R.sub.2 and R.sub.3 are as defined above, with sulphuric acid to obtain a compound of formula ##STR18##wherein R.sub.7 is H and R.sub.10 and R.sub.11 are as defined above, in form of a crystalline sulphuric acid addition salt, and,d. converting a sulphuric acid addition salt of 7-[2-(aminothiazol-4-yl)-2-(carboxy-methoxyimino)acetamido]-3-vinyl-3-ceph em-4-carboxylic acid of formula IIA, wherein R.sub.7 is H and R.sub.10 and R.sub.11 are as defined above, into cefixime of formula II, and optionallye. removing R.sub.11 if other than hydrogen ##STR19##