Prepn. of cephalosporin derivs. comprises acylatng the 7-amino cpds. of formula (I): (X=acetoxy; 5-methyl-1,3,4-thiadiazol-5-ylthio; or 1-methyl-1H-tetrazol-5-ylthio) with crude or distilled acyl halides (II). (I) are dissolved in water at 0-30 degrees C then (II), dissolved in a water-immiscible solvent, added. Pref. (I) is dissolved in water or pH 7-8 buffer with addition of a stoichiometric amt. of organic or inorganic base, e.g. NaOH, KOH, or aliphatic tert, amines so that the final pH is 6-8.5. During acylation the pH is held at 6-8 by adding a mild base, e.g. NaHCO3. Used for making antibiotics such as cefazolin; cefamandal-nafate; 7-phenylacetamido-, 7- 1-1H-tetrazolylacetamido - or 7- R-(-)-formyloxy-phenylacetamido -cephalosporanic acids, or esp. cephalotin. Hydrolysis of (II) by the water is prevented so yields are improved.
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