In the production of a semi-synthetic .beta.-lactam antibiotic by reacting an amino compound of the formula ##STR1## in which X is the remaining members of a ring of a .beta.-lactam antibiotic, andR is a hydrogen atom or a methoxy group,with an activated carboxylic acid derivative of the formula ##STR2## in which R.sub.1 is an organic radical,B is an optionally substituted phenyl, cyclohexadienyl or heterocyclyl radical andR.sub.2 is a lower alkyl radical,the improvement which comprises effecting the reaction in an acetone/water mixture which contains acetone and water in a volume ratio of about 0.5:1 to 3:1. Advantageously the reaction is carried out at about -10.degree. to +10.degree. C. in the presence of an organic base employing about 1.1 to 1.2 mols of the amino compound per mol of the activated carboxylic acid derivative.