Phosphorus oxychloride → Chloro-N,N-dimethylformiminium chloride

Participants

Reaction Steps

Vilsmeier reagent was prepared from phosphorus oxychloride (1.2 g) and N,N-dimethylformamide (0.6 g) in ethyl acetate (2.4 ml) in a usual manner. 2-(2-Formamido-5-chlorothiazol-4-yl)-2-tert-butoxycarbonylmethoxyiminoacetic acid (syn isomer) (2.4 g) was added to the stirred suspension of Vilsmeier reagent in dry tetrahydrofuran (24 ml) under ice-cooling and stirred for 20 minutes at same temperature [Solution A]. N-Trimethylsilylacetamide (6.4 g) was added to the stirred suspension of 7-amino-3-(1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid (2.0 g) in tetrahydrofuran (40 ml), and the mixture was stirred for 30 minutes at 35° to 40° C. To the solution was added the solution [Solution A] at -10° C., and the resulting solution was stirred at same temperature for 30 minutes. Water and ethyl acetate were added to the reaction mixture at -10° C. The organic layer was separated and added to water. The mixture was adjusted to pH 7.5 with a saturated aqueous solution of sodium bicarbonate. The aqueous layer was separated and adjusted to pH 2.0 with 10% aqueous hydrochloric acid, and then extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate and evaporated in vacuo to give 7-[2-(2-formamido-5-chlorothiazol-4-yl)-2-tert-butoxycarbonylmethoxyiminoacetamido]-3-(1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer) (3.72 g).

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