Phosphorus oxychloride → Chloro-N,N-dimethylformiminium chloride

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Reaction Steps

Vilsmeier reagent was prepared from phosphorus oxychloride (1.7 g) and N,N-dimethylformamide (0.8 g) in ethyl acetate (3.2 ml) in a usual manner. 2-tert-Butoxycarbonylmethoxyimino-2-(1,2,4-thiadiazol-3-yl)acetic acid (syn isomer) (2.7 g) was added to a stirred suspension of the Vilsmeier reagent prepared above in ethyl acetate (30 ml) under ice-cooling, and the stirring was continued for 40 minutes at the same temperature to produce an activated acid solution. Bis(trimethylsilyl)urea (5.8 g) was added to a stirred suspension of p-nitrobenzyl 7-amino-3-chloro-3-cephem-4-carboxylate hydrochloride (3.8 g) in tetrahydrofuran (40 ml), and the mixture was stirred for 20 minutes at 35° to 40° C. To this solution was added the above activated acid solution at -10° C., followed by stirring for 20 minutes at the same temperature. After water and ethyl acetate were added to the reaction mixture, the separated organic layer was washed with a saturated aqueous sodium bicarbonate and aqueous sodium chloride, and then dried over magnesium sulfate. The solution was evaporated to give p-nitrobenzyl 7-[2-tert-butoxycarbonylmethoxyimino-2-(1,2,4-thiadiazol-3-yl)acetamido]-3-chloro-3-cephem-4-carboxylate (syn isomer) (4.97 g).

Provenance & Evidence