MANUFACTURE OF CEPHALOSPORIN DERIVATIVE

A process for the manufacture of a cephalosporin derivative of the formula I: in which X is sulphur, oxygen or sulphinyl; R is any one of the C-3 substituents from antibacterially-active cephalosporins known in the art; R is hydrogen or 1-6C alkyl; R is hydrogen or 1-6C alkyl; and the pharmaceutically-acceptable acid-addition and base-addition salts thereof, characterised by cyclisation of a compound of the formula II: or a derivative thereof in which the carbonyl group is masked, or an acid-addition salt thereof, in which R and R individually have one of the values for R and R , R is a nitrogen-protecting group and R is hydrogen or any one of the cephalosporin 3-carboxylic acid protecting groups known in the art; whereafter when the product from the cyclisation reatains the protecting group R (when R is other than hydrogen) the protecting group R is replaced by hydrogen by conventional means; and whereafter when the compound of the formula I is obtained in the form of the free base or salt, and a pharmaceutically-acceptable salt or free base respectively is required, any necessary conversion between free base and salt is carried out by conventional means.