Phosphorus oxychloride → Chloro-N,N-dimethylformiminium chloride

Participants

Reaction Steps

Vilsmeier reagent was prepared from N,N-dimethylformamide (0.45 g.) and phosphoryl chloride (1.03 g.) in a usual manner. 2-(2-Formamidothiazol-4-yl)-2-(2-tert-butoxycarbonylaminoethoxyimino)acetic acid (syn isomer, 2.0 g.) was added to the stirred suspension of the Vilsmeier reagent in ethyl acetate (40 ml.) under ice cooling and stirred at the same temperature for 30 minutes [Solution A]. Trimethylsilylacetamide (5.9 g.) was added to a stirred suspension of 7-amino-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (1.8 g.) in ethyl acetate (30 ml.), and the mixture was stirred at the room temperature for 30 minutes. To the solution was added the solution A all at once at -30° C., and the resultant solution was stirred at -10° to -40° C. for an hour. Water and ethyl acetate (100 ml.) were added to reaction mixture at -10° C. and, the ethyl acetate layer was separated. Water (100 ml.) was added to the ethyl acetate solution, and adjusted to pH 7.0 with a saturated sodium bicarbonate aqueous solution. After the aqueous layer was separated, ethyl acetate was added thereto. The mixture was adjusted to pH 3.0 with 10% hydrochloric acid under ice-cooling. The ethyl acetate layer was washed with a saturated sodium chloride aqueous solution, dried over magnesium sulfate and evaporated in vacuo. The residue was pulverized with diisopropyl ether, collected by filtration to give 7-[2-(2-formamidothiazol-4-yl)-2-(2-tert-butoxycarbonylaminoethoxyimino)acetamido]-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer, 2.8 g.).

Provenance & Evidence