Phosphorus pentachloride → Benzhydryl 7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetamido]-3-chloromethyl-3-cephem-4-carboxylate

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Reaction Steps

To a stirred suspension of 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetic acid (III-1), (2.1 g, 10 mmole) in dry CH2Cl2 (50 ml) was added PCl5 (2.09 g, 10 mmole) at -30° C., and the mixture was stirred for 20 minutes at -15° to -20° C. To the above acid chloride solution was added a solution of diphenylmethyl 7-amino-3-chloromethyl-3-cephem-4-carboxylate hydrochloride (II) (4.5 g, 10 mmole) in CH2Cl2 (50 ml) containing N,O-bis-(trimethylsilyl)acetamide (10 g, 50 mmole) at -30° C. After stirring at -10° C. for 1 hour, the mixture was concentrated to remove the CH2Cl2 and diluted with ethyl acetate (200 ml). The mixture was washed with 10% aqueous NaHCO3 (2×40 ml), H2O (2×20 ml) and brine (10 ml), successively, and dried over MgSO4. The solvent was evaporated in vacuo and the resulting oily residue (10 g) was dissolved in CHCl3 (20 ml) and chromatographed on a silica gel (Wako gel C-200, 100 g containing 10 ml of 1/1.5M pH 7 phosphate buffer) using 1-3% CH3OH--CHCl3. Fractions containing the title compound were evaporated to give 5.7 g (95%) of IV-1 as a yellow amorphous powder. M.p. >140° C. (dec.).

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