Water → HCID 131711121, compound

Participants

Reaction Steps

3-(N-tert-butoxycarbonylamino)-3-(2-thienyl)-DL-propionic acid (10.8 g.) and triethylamine (4.04 g.) were dissolved in dry acetone (200 ml.) with stirring at room temperature. On cooling the solution at -10° to -15° C, pivaloyl chloride (4.82 g.) was added to the solution all at once with stirring. The mixture was stirred at -10° to -15° C for an hour and then cooled to -40° to -50° C. To the mixture was added a mixture of 7-amino-3-(5-methyl-1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid (13.76 g.), triethylamine (12.0 g.), water (40 ml.) and acetone (160 ml.) all at once. The resultant mixture was stirred at -40° to -50° C for 1.5 hours and then at room temperature for 2 hours. The acetone was removed from the reaction mixture under reduced pressure and the residue was washed with ethyl acetate. The aqueous layer was separated, adjusted with 10% hydrochloric acid to pH 1 and extracted with ethyl acetate. The extract was washed with water and an aqueous solution of sodium chloride, dried over magnesium sulfate, treated with activated charcoal and then concentrated under reduced pressure. Ether was added to the concentrate and the mixture was stirred for 3 hours. The precipitate was filtered to give 7-[3-(N-tert-butoxycarbonylamino)-3-(2-thienyl)-DL-propionamido[-3-(5-methyl-1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid (15.1 g.), m.p. 130° to 135° C (dec.).

Provenance & Evidence