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

Process for the manufacture of a member selected from the group consisting of 7-N-R.sub.1.sup.2 -N-R.sub.1.sup.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.sub.1.sup.b is hydrogen, R.sub.1.sup.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.sub.1.sup.c denotes hydrogen or, if n represents 0, denotes .alpha.-poly-branched lower alkoxycarbonylamino, phenyl-lower alkoxycarbonylamino or phenyl-lower alkoxycarbonylamino substituted by lower alkoxy, nitro, or hydroxyl, .alpha.-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.sub.2 denotes hydrogen, lower alkyl, .alpha.-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.sub.2 represents hydrogen, or with inorganic acids or organic sulfonic acids, if R.sub.1.sup.a and R.sub.1.sup.b both represent hydrogen or inner salts of such compounds, if R.sub.2, R.sub.1.sup.a and R.sub.1.sup.b all represent hydrogen, wherein a 7- (N-R.sub.1.sup.A -N-R.sub.1.sup.b -amino)-3-Y-methyl-2-cephem-4-carboxylic acid compound of the formula ##STR8## wherein R.sub.1.sup.b and R.sub.2 have the above-mentioned meanings, R.sub.1.sup.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.