Phosphorus oxychloride → benzhydryl 7beta-[2-cyclopropyloxyimino-2-(2-formamidothiazol-4-yl)acetamido]-3-[(Z)-2-(3-pyridyl)vinylthiomethyl]-3-cephem-4-carboxylate

Participants

Reaction Steps

Phosphorus oxychloride (0.256 ml) was added to a solution of N,N-dimethylformamide (0.212 ml) in ethyl acetate (0.6 ml) under ice-cooling and the mixture was stirred at the same temperature for 10 minutes. To the mixture was added tetrahydrofuran (13 ml) and the mixture was stirred under ice-cooling for additional 10 minutes. To the mixture was added 2-cyclopropyloxyimino-2-(2-formamidothiazol-4-yl)acetic acid (syn isomer) (540 mg) and the mixture was stirred for 30 minutes under ice-cooling to give an activated acid solution. On the other hand, benzhydryl 7β-amino-3-[(Z)-2-(3-pyridyl)vinylthiomethyl]-3-cephem-4-carboxylate (1.03 g) was dissolved in a solution of bis(trimethylsilyl)acetamide (20 ml) in tetrahydrofuran (15 ml). To the solution was added the activated acid solution obtained above at -30° C. and the mixture was stirred for 30 minutes at -20° C. to -10° C. The mixture was poured into a mixture of ice-water (50 ml) and ethyl acetate (70 ml) and adjusted to pH 7 with saturated aqueous solution of sodium bicarbonate. The organic layer was separated, washed with saturated aqueous solution of sodium chloride, dried over magnesium sulfate and concentrated in vacuo. The residue was triturated with diethyl ether to give benzhydryl 7β-[2-cyclopropyloxyimino-2-(2-formamidothiazol-4-yl)acetamido]-3-[(Z)-2-(3-pyridyl)vinylthiomethyl]-3-cephem-4-carboxylate (syn isomer) (820 mg).

Provenance & Evidence