Phosphorus oxychloride → Benzhydryl 7-[2-(6-formamidopyridin-2-yl)-2-tert-butoxycarbonylmethoxyiminoacetamido]-3-ethylthio-3-cephem-4-carboxylate

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Reaction Steps

Vilsmeier reagent prepared from phosphorus oxychloride (0.52 ml) and N,N-dimethylformamide (0.44 ml) was suspended in dry tetrahydrofuran (16.5 ml). To the stirred suspension was added 2-(6-formamidopyridin-2-yl)-2-tert-butoxycarbonylmethoxyiminoacetic acid (syn isomer, 1.67 g) under ice-cooling and then the solution was stirred for an hour at the same temperature to prepare the activated acid solution. To the solution of benzhydryl 7-amino-3-ethylthio-3-cephem-4-carboxylate hydrochloride (2.0 g) and monotrimethylsilylacetamide (5.67 g) in methylene chloride (40 ml) was added the activated acid solution all at once at -20° C., and then the mixed solution was stirred for an hour at -20° to -10° C. To the resultant solution were added water (50 ml) and ethyl acetate (100 ml). The organic layer was separated and washed with 5% aqueous solution of sodium bicarbonate. The solution was washed with a saturated aqueous solution of sodium chloride and dried over magnesium sulfate. The solvent was evaporated under reduced pressure to give benzhydryl 7-[2-(6-formamidopyridin-2-yl)-2-tert-butoxycarbonylmethoxyiminoacetamido]-3-ethylthio-3-cephem-4-carboxylate (syn isomer, 2.5 g), mp. 113° to 123° C.

Provenance & Evidence