Hydrochloric Acid → Chloro-N,N-dimethylformiminium chloride

Participants

Reaction Steps

Vilsmeier reagent was prepared from phosphorus oxychloride (1.6 g) and N,N-dimethylformamide (0.8 g) in ethyl acetate (3.2 ml) in a usual manner. 2-t-Butoxycarbonylmethoxyimino-2-(4-thiazolyl)acetic acid (syn isomer) (2.5 g) was added to the stirred suspension of Vilsmeier reagent in ethyl acetate (20 ml) under ice-cooling and the resultant mixture was stirred for 20 minutes at the same temperature to produce an activated acid solution. 7-Amino-3-(tetrazolo[1,5-b]-pyridazin-6-yl)thiomethyl-3-cephem-4-carboxylic acid (3.5 g) was dissolved in a solution of sodium bicarbonate (2.4 g) in a mixture of water (26 ml) and acetone (26 ml). To the solution was added the activated acid solution obtained above at -3° to 3° C. and the solution was stirred for 30 minutes under keeping the pH 7 to 8 with 20% aqueous solution of sodium carbonate. Water and ethyl acetate were added to the reaction mixture and the mixture was adjusted to pH 2.0 with 10% hydrochloric acid. The separated organic layer was washed with saturated aqueous solution of sodium chloride, dried over magnesium sulfate and evaporated to give 7-[2-t-butoxycarbonylmethoxyimino-2-(4-thiazolyl)acetamido]-3-(tetrazolo[1,5-b]pyridazin-6-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer) (3.7 g).

Provenance & Evidence