Phosphorus oxychloride → 7-[2-methoxyimino-2-(2-formamidothiazol-4-yl)acetamido]-3-(1-hexyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

The Vilsmeier reagent was prepared from dry dimethylformamide (1.0 g.), dry ethyl acetate (4 ml.) and phosphorus oxychloride (2.1 g.) by the conventional method. Dry ethyl acetate (45 ml.) and 2-methoxyimino-2-(2-formamidothiazol-4-yl)acetic acid (syn isomer) (2.85 g.) were added thereto. This solution was added at -10° C. to a stirred solution, which was prepared by stirring for 1 hour at 40° C. a mixture of 7-amino-3-(1-hexyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (4.5 g.), trimethylsilylacetamide (10.4 g.) and dry ethyl acetate (90 ml.), and the resulting mixture was stirred for 1.5 hours at -5° to -10° C. Water (50 ml.) was added to the reaction mixture and the ethyl acetate layer was separated. Water (40 ml.) was added thereto and the mixture was adjusted to pH 7.0 with a saturated aqueous solution of sodium bicarbonate. The aqueous layer was separated, washed with ethyl acetate and adjusted to pH 2.5 with 10% hydrochloric acid. Precipitates were collected by filtration, washed with water and dried under reduced pressure to give powder to 7-[2-methoxyimino-2-(2-formamidothiazol-4-yl)acetamido]-3-(1-hexyl- 1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer) (6.18 g.).

Provenance & Evidence