Hydrochloric Acid → Chloro-N,N-dimethylformiminium chloride

Participants

Reaction Steps

Vilsmeier reagent was prepared from phosphorus oxychloride (1.4 g) and dimethyl formamide (0.67 g) in ethyl acetate (2.68 ml) in usual manner. 2-(5-Chloro-2-formamidothiazol-4-yl)-2-t-butoxycarbonylmethoxyiminoacetic acid (syn isomer) (2.8 g) was added to the stirred suspension of Vilsmeier reagent in tetrahydrofuran (30 ml) under ice cooling and stirred for 20 minutes at same temperature to produce an activated solution. N-(trimethylsilyl)acetamide (6.4 g) was added to the stirred suspension of 7-amino-3-methyl-3-cephem-4-carboxylic acid (1.5 g) in tetrahydrofuran (30 ml), and stirred for 20 minutes at 35° C. to 40° C. To the solution was added the above activated solution at -10° C. and stirred at same temperature for 30 minutes. Water and ethyl acetate were added to the reaction mixture and the separated organic layer was added to water and the mixture was adjusted to pH 7.5 with saturated aqueous sodium bicarbonate. The separated aqueous layer was adjusted to pH 2.0 with 10% aqueous hydrochloric acid and extracted with ethyl acetate. The extract layer was washed with saturated aqueous sodium chloride, dried over magnesium sulfate and evaporated to give 7-[2-(5-chloro-2-formamidothiazol-4-yl)-2-t-butoxycarbonylmethoxyiminoacetamido]-3-methyl-3-cephem-4-carboxylic acid (syn isomer) (3.03 g).

Provenance & Evidence