Process for the manufacture of 3-substituted thiomethyl-7-amino-2-cephem-4-carboxylic acid compound

Claim 1

Process for the manufacture of a member selected from the group consisting of 7-N-R 1 2 -N-R 1 b -amino-3-R-thiomethyl-2-cephem-4 carboxylic acid compounds of the formula ##STR6## wherein R represents methyl, thiadiazolyl, tetrazolyl, methyl-substituted thiadiazolyl, or methyl-substituted tetrazolyl, R 1 b is hydrogen, R 1 a represents hydrogen, cyanoacetyl or an acyl radical of the formula ##STR7## wherein Ar is phenyl or tetrazolyl, X is oxygen, n denoted 0 or 1 and R 1 c denotes hydrogen or, if n represents 0, denotes α-poly-branched lower alkoxycarbonylamino, phenyl-lower alkoxycarbonylamino or phenyl-lower alkoxycarbonylamino substituted by lower alkoxy, nitro, or hydroxyl, α-poly-branched lower alkoxycarbonyloxy, 2-halogeno-lower alkoxycarbonyloxy, or formyloxy, or represents a 5-amino-5-carboxyvaleryl radical, wherein the amino and/or carboxyl group are optionally present, as lower alkanoylamino, dichloro-acetylamino, or phthaloylamino, or as phenyl-lower alkoxy-carbonyl, and R 2 denotes hydrogen, lower alkyl, α-poly-branched lower alkyl, or 2 halogeno-lower alkyl, nitrobenzyl, diphenylmethyl or lower alkoxy-substituted diphenylmethyl, and salts of such compounds with alkali and alkaline earth metals, ammonia or organic amines, if R 2 represents hydrogen, or with inorganic acids or organic sulfonic acids, if R 1 a and R 1 b both represent hydrogen or inner salts of such compounds, if R 2 , R 1 a and R 1 b all represent hydrogen, wherein a 7- (N-R 1 A -N-R 1 b -amino)-3-Y-methyl-2-cephem-4-carboxylic acid compound of the formula ##STR8## wherein R 1 b and R 2 have the above-mentioned meanings, R 1 A represents trityl, tri-lower alkyl silyl, phenylglycyl, phenylacetyl or phenoxyacetyl , and Y represents hydroxy, lower alkanoyloxy or halogeno acetoxy, is reacted with a compound of the formula R-SH (III), in the presence of trifluoroacetic acid with the proviso that when Y represents trifluoroacetoxy, the reaction can be carried out in the absence of trifluoroacetic acid.