Process for the preparation of a 3-substituted thio-3-cephem compound

A process for the preparation of a 3-substituted thio-3-cephem compound of structure (5) ##STR24## wherein R.sup.1 is an acyl group;

• R.sup.2 is a carboxyl-protecting group;
• and R.sup.4 is a lower alkyl group, a cycloalkyl group or a heterocyclic group or a heterocyclic group-substituted methyl group, which comprises the steps of reacting a 3-acylthio-cephem compound of structure (1) ##STR25## wherein R.sup.1 and R.sup.2 each have the meaning as defined above;
• R.sup.3 is a lower alkyl group containing up to 6 carbon atoms, an aryl group or a substituted aryl group, said alkyl or aryl group being such that the acyl group --COR.sup.3 containing said alkyl or aryl group as R.sup.3 is reactable with tertiary amine (2) and secondary amine as defined below;
• and the dotted line given in the formula (1) represents that the compound of formula (1) is either a compound having a .DELTA..sup.2 double bond present in the 6-membered ring or a compound having a .DELTA..sup.3 double bond present in the 6-membered ring or a mixture of the compounds of these two types, with a tertiary amine of structure (2) ##STR26## wherein R.sup.5, R.sup.6 and R.sup.7 are the same or different and individually represents lower alkyl group;
• or R.sup.5 is a lower alkyl group and R.sup.6 and R.sup.7 taken together with a nitrogen atom to which R.sup.6 and R.sup.7 are attached form a nitrogen-containing heterocyclic ring having or not having an oxygen atom as a hetero atom, and also with a secondary amine to give a compound of structure (3) ##STR27## wherein R.sup.1, R.sup.2, R.sup.5, R.sup.6 and R.sup.7 each having the meanings as defined above;
• and the dotted line given in the formula (3) also has the meaning as defined above;
• and then reacting the compound of structure (3) thus formed with a compound of structure (4)
• R.sup.4 --X (4)
• wherein R.sup.4 has the meaning as defined above;
• and X is selected from the group consisting of halogen, methanesulfonyloxy, p-toluenesulfonyloxy, trifluoromethanesulfonlyloxy and alkoxysulfonyloxy, to form the 3-substituted thio-3-cephem compound of structure (5) above.