Phosphorus oxychloride → Chloro-N,N-dimethylformiminium chloride

Participants

Reaction Steps

Vilsmeier reagent was prepared from phosphorus oxychloride (10.1 g) and dimethylformamide (4.8 g) in ethyl acetate (16 ml) in a usual manner. 4-Chloro-2-methoxycarbonylmethoxyimino-3-oxobutyric acid (syn isomer) (15.7 g) was added to the stirred suspension of Vilsmeier reagent in ethyl acetate (116 ml) under ice-cooling and the mixture was stirred at this temperature for 30 minutes to give an activated acid solution. To a solution of benzhydryl 7-amino-3-methylthio-3-cephem-4-carboxylate, hydrochloride (26.9 g) and trimethylsilylacetamide (42 g) in ethyl acetate (300 ml) was added the above activated acid solution at -20° C., and the mixture was stirred at -20° to 0° C. for one hour. To the reaction mixture was added water (200 ml) and the ethyl acetate layer was separated. The ethyl acetate layer was washed with saturated sodium bicarbonate solution and brine, and dried over magnesium sulfate. The solution was evaporated and the residue was triturated with ether to give benzhydryl 7-(4-chloro-2-methoxycarbonylmethoxyimino-3-oxobutyramido]-3-methylthio-3-cephem-4-carboxylate (syn isomer) (35.7 g).

Provenance & Evidence