Pyridine → Benzhydryl 7-amino-3-cephem-4-carboxylate

Participants

Reaction Steps

To a suspension of 3-hydroxy-7beta-phenylacetylaminocepham-4-carboxylic acid diphenylmethyl ester (3e) in dichloromethane (13 parts) cooling at -5° to 0° C. under nitrogen are added at -5° to 0° C. pyridine (3 equivalents) and at -20° to -25° C. phosphorus pentachloride (2.7 equivalents). After stirring at -15° to -10° C. for 4 hours, the mixture is diluted with methanol (20 parts) cooled at -40° to -30° C. and stirred for 3 hours at -10° to -15° C. The mixture is cooled to -20° to -25° C., mixed dropwise with triethylamine (12 equivalents), and kept at 0° to 5° C. overnight. The mixture is diluted with ice-water (20 parts) and stirred at 0° to 5° C. for 20 minutes. The formed organic layer is washed with hydrochloric acid, water, aqueous sodium hydrogen carbonate, and water, dried, and concentrated. The residue is crystallized from ethyl acetate to give 7beta-amino-3-cephem-4-carboxylic acid diphenylmethyl ester (5). Yield: 47.3%.

Provenance & Evidence