Phosphorus oxychloride → Chloro-N,N-dimethylformiminium chloride

Participants

Reaction Conditions

Reaction Steps

The solution of Vilsmeier reagent was prepared from dry N,N-dimethylformamide (0.48 g), phosphoryl chloride (1.0 g), ethyl acetate (4 ml) and tetrahydrofuran (15 ml) in a usual manner. To the solution was added 2-(2-cyclopenten-1-yl)oxyimino-2-[2-(2,2,2-trifluoroacetamido)thiazol-4-yl]acetic acid (syn isomer)(1.9 g) under ice cooling and the resulting solution was stirred for 30 minutes (Solution A). A mixture of N-[7-amino-3-cephem-3-ylmethyl]pyridinium-4-carboxylate dihydrochloride (2.0 g), trimethylsilylacetamide (5.7 g) and tetrahydrofuran (40 ml) was warmed to 40° C. and stirred to give a homogeneous solution, which was cooled to -25° C. and then thereto was added Solution A. The resulting mixture was stirred for 30 minutes around -10° C. To the reaction mixture containing N-[7-[2-(2-cyclopenten-1-yl)oxyimino-2-{2-(2,2,2-trifluoroacetamido)thiazol-4-yl}acetamido]-3-cephem-3-ylmethyl]pyridinium-4-carboxylate (syn isomer) were added ethyl acetate (50 ml) and water (100 ml). The ethyl acetate layer was separated and extracted with a saturated aqueous solution of sodium bicarbonate (50 ml). The extract and the remaining aqueous layer was combined, adjusted to pH 6.0 with 4 N aqueous solution of sodium hydroxide and then thereto was added sodium acetate (7.5 g). The mixture was stirred for 41 hours at room temperature, adjusted to pH 2.0 with 10% hydrochloric acid, and then filtered. The filtrate was subjected to column chromatography (non-ion adsorption resin, Diaion HP20 prepared by Mitsubishi Chemical Industries)(60 ml) and the column was washed with water and then eluted with 10% isopropyl alcohol and 30% methanol. The eluates containing the object compound were collected, evaporated and lyophilized. The obtained powder was dried over phosphorous pentoxide under reduced pressure to give N-[7-{2-(2-cyclopenten-1-yl)oxyimino-2-(2-amino-thiazol-4-yl)acetamido}-3-cephem-3-ylmethyl]pyridinium-4-carboxylate (syn isomer)(0.3 g). mp. 171° to 180° C. (dec.).

Provenance & Evidence