Phosphorus oxychloride → 7-[2-Methoxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)acetamido]-3-carbamoyloxymethyl-3-cephem-4-carboxylic acid

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Reaction Steps

A mixture of 2-methoxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)acetic acid (syn isomer)(1.01 g) and phosphorus oxychloride (3.06 g) in methylene chloride (25 ml) was stirred for 2 hours at ambient temperature, cooled to 0° C. and thereto was added N,N-dimethylformamide (2.0 ml), followed by stirring for an additional 45 minutes at 0° C. A mixture of 7-amino-3-carbamoyloxymethyl-3-cephem-4-carboxylic acid (4.9 g) and trimethylsilylacetamide (11 g) in methylene chloride (100 ml) was warmed to make a clear solution. The solution was cooled to -15° C. and added to the above obtained solution, followed by stirring for 30 minutes at 0° C. The reaction mixture was poured into a cold aqueous solution of sodium bicarbonate. The aqueous layer was separated and thereto was added ethyl acetate. The resulting mixture was adjusted to pH 2 with 10% hydrochloric acid, filtered to remove an insoluble material and then saturated with sodium chloride. The ethyl acetate layer was separated, dried over magnesium sulfate and evaporated. The residue was triturated with diethyl ether to give a crude product of the title compound (1.2 g). The crude material was dissolved in an aqueous solution of sodium bicarbonate, and reprecipitated with 10% hydrochloric acid. The precipitates were collected by filtration, washed with water and dried to give the title compound (0.35 g), mp. 185° to 190° C. (dec.).

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