Phosphorus oxychloride → Chloro-N,N-dimethylformiminium chloride

Participants

Reaction Steps

Vilsmeier reagent was prepared from phosphorus oxychloride (14.4 g) and N,N-dimethylformamide (6.9 g) in ethyl acetate (27.6 ml) in a usual manner. 2-t-Butoxycarbonylmethoxyimino-2-(4-thiazolyl)acetic acid (syn isomer) (22.8 g) was added to the stirred suspension of Vilsmeier reagent in ethyl acetate (200 ml) under ice-cooling and the mixture was stirred for 20 minutes at the same temperature to produce an activated acid solution. Trimethylsilylacetamide (56.9 g) was added to a stirred suspension of benzhydryl 7-amino-3-chloromethyl-3-cephem-4-carboxylate (30 g) in ethyl acetate (300 ml) and the resultant mixture was stirred for 30 minutes at ambient temperature. To the solution was added the activated acid solution obtained above at -10° C. and the mixture was stirred for 30 minutes at the same temperature. Water was added to the reaction mixture, and the separated organic layer was washed with a saturated aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride, successively. The ethyl acetate layer was dried over magnesium sulfate and evaporated to give benzhydryl 7-[2-t-butoxycarbonylmethoxyimino-2-(4-thiazolyl)acetamido]-3-chloromethyl-3-cephem-4-carboxylate (syn isomer) (37.3 g).

Provenance & Evidence