Patent ID: 6906187

Claim:
A process for the preparation of a 3-disubstituted cepham-4-carboxylic acid derivative of formula I wherein R″ is 4-methoxybenzyl, X is the residue of a thioether selected from the group consisting of phenyl; phenyl substituted on the benzene ring with a methyl or methoxy group; benzyl; benzyl substituted on the benzene ring with a methyl or methoxy group; and methyl radicals and Z is the residue of a nucleophilic compound selected from the group consisting of 2-furoylthio, acetoxy and 1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-1,2,4-triazin-3-ylthio radicals, which process comprises (i) reacting a functional derivative of the α-(2-chloroacetamido)thiazol-4-yl-α-methoxyiminoacetic acid of formula II selected from the group consisting of acid halides, anhydride, mixed anhydrides, active esters and an acid activated with a reagent selected from the group consisting of dicyclohexylcarbodiimide, mercaptobenzotriazole and benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate, with a 7β-amino-3-methylenecepham-4-carboxylic acid derivative of formula III wherein R″ is 4-methoxybenzyl, or with an addition salt thereof; (ii) treating the corresponding 4-methoxybenzyl 7β-[α-(2-chloroacetamido)thiazol-4-yl-α-methoxyimino]acetamido-3-methylenecepham-4-carboxylate thus obtained of formula IV wherein R″ is 4-methoxybenzyl, with a S-chloromercaptan of formula X—S—Cl, in which X is as defined above; and (iii) reacting the corresponding 4-methoxybenzyl 7β-[α-(2-chloroacetamido)thiazol-4-yl-α-methoxyimino]acetamido-3-thio-3chloromethylcepham-4carboxylate thus obtained of formula V wherein R″ and X are as defined above, with a compound of formula M-Z, in which M is an alkaline metal or a hydrogen atom and Z is the residue of a nucleophilic compound selected from the group consisting of the 2-furoylthio, acetoxy and 1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-1,2,4-triazin-3-ylthio radicals.