Phosphorus pentachloride → 7-[2-tert-butoxycarbonylmethoxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)acetamido]-3-[1-(2-propynyl)-1H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of phosphorus pentachloride (2.50 g) in methylene chloride (60 ml) was added 2-tert-butoxycarbonylmethoxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)acetic acid (syn isomer)(3.02 g) at -15° C. and the mixture was stirred for 45 minutes at -10° to -13° C. On the other hand, a mixture of 7-amino-3-[1-(2-propynyl)-1H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylic acid (3.52 g) and trimethylsilylacetamide (10 g) in methylene chloride (50 ml) was warmed to make a clear solution and then cooled to -10° C. The solution was added to the above activated mixture at a time and the mixture was stirred for 15 minutes at -5° to 10° C. The reaction mixture was poured into an aqueous solution (120 ml) of sodium bicarbonate (6.7 g) and stirred for 30 minutes at room temperature. The aqueous layer was separated and ethyl acetate was added thereto. The resulting mixture was adjusted to pH 3 with 6 N hydrochloric acid. The ethyl acetate layer was separated, dried over magnesium sulfate and then evaporated. The residue was pulverized with isopropyl ether and then dried to give 7-[2-tert-butoxycarbonylmethoxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)acetamido]-3-[1-(2-propynyl)-1H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylic acid (syn isomer)(3.8 g), mp. 120° to 125° C. (dec.).

Provenance & Evidence