Sodium Iodide → Benzhydryl 7-Benzylideneamino-3-[3-(4-carbamoyl-1-pyridinio)-1-propen-1-yl]-3-cephem-4-carboxylate Iodide

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Reaction Steps

To a chilled mixture of the 3-chloropropenylcephem XVII (Z isomer) (16.4 g) in acetone (5 ml), was added dropwise a solution of sodium iodide (6.3 g, 42 mmole) in acetone (30 ml) over 10 minutes under nitrogen atmosphere, and the mixture was stirred at room temperature. The reaction was monitored by the ratio of uv absorption [E1 cm1% (255 nm)/E1 cm1% (320 nm)]. When the ratio reached below 1.30 (after 45 minutes), the mixture was diluted with carbon tetrachloride (400 ml), and allowed to stand at room temperature. When the ratio came to below 1.10 (after 3 hours), the mixture was concentrated to a half its volume. The concentrate was treated with a small amount of charcoal and diatomaceous earth, and filtered. The filter cake was washed with a 1:1 mixture (100 ml) of methylene chloride and carbon tetrachloride. To the combined solution of the filtrate and washings, was added a solution of isonicotinamide (3.5 g, 28.7 mmole) in dimethylformamide (20 ml) and the mixture was concentrated under reduced pressure. The concentration was allowed to stand at room temperature for 1.5 hours and washed with isopropyl ether (100 ml×3). The residual brown semi-solid was dissolved in methylene chloride (50 ml) and the solution was added dropwise, with stirring, to ethyl acetate (1.5 L). The resulting precipitate was collected by filtration and washed with ethyl acetate (200 ml). After drying over phosphorous pentoxide in vacuo, 17 g of the title compound XXI-H (E isomer) was obtained. Yellow amorphous powder. M.p. 150°-155° C. (dec.). Estimated purity 80% by nmr.

Provenance & Evidence