Phosphorus oxychloride → Chloro-N,N-dimethylformiminium chloride

Participants

Reaction Steps

Vilsmeier reagent was prepared from N,N-dimethylformamide (0.44 g.) and phosphoryl chloride (0.92 g.) in an usual manner. 2-(2-Formamidothiazol4-yl)-2-(4-bromo-3-hydroxybenzyloxyimino)acetic acid (syn isomer, 2.0 g.) was added to the stirred suspension of Vilsmeier reagent in ethyl acetate (18 ml.) under ice-cooling, and stirred at the same temperature for 30 minutes to give a solution [hereinafter referred to solution A]. Trimethylsilylacetamide (3.9 g.) was added to a stirred suspension of 7-amino-3-cephem-4-carboxylic acid (1.0 g.) in ethyl acetate (10 ml.) and the mixture was stirred at 40° C. for 30 minutes. To the solution was added the solution A all at once at -30° C., and stirred at -10° to -20° C. for an hour. Water (100 ml.) and ethyl acetate (100 ml.) were added to the resultant mixture at -10° C. After separating the organic layer, water (100 ml.) was added to the organic layer and adjusted to pH 7.0 with a sodium bicarbonate saturated solution. The aqueous layer was separated, and ethyl acetate was added thereto. The mixture was adjusted to pH 3.0 with 10% hydrochloric acid under ice-cooling. The organic layer was separated, washed with a sodium chloride saturated solution and dried over magnesium sulfate. The solution was concentrated in vacuo to give 7-[2-(2-formamidothiazol-4-yl)-2-(4-bromo-3-hydroxybenzyloxyimino)acetamido]-3-cephem-4-carboxylic acid (syn isomer, 2.0 g.).

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