Pyridine → HCID 13127405, compound

Participants

Reaction Steps

A stirred suspension of phosphorus pentachloride (156 g, 0.75 mole) in dry dichloromethane (1.5 liters) was cooled in an ice-bath and treated with pyridine (60.5 ml, 0.75 mole) at such a rate that the temperature of the mixture remained at ca. 20° to 25°. The mixture was stirred and cooled to 8° and diphenylmethyl (6R,7R)-7-(thien-2-yl)acetamido-3-trichloroacetylcarbamoyloxymethylceph-3-em-4-carboxylate (354.5 g, 0.5 mole) was added in portions over 10 minutes. The mixture was stirred at ca. 8° for 1.75 hours and then added over 10 minutes to a stirred mixture of butane-1,3-diol (225 ml, 2.5 mole) and dichloromethane (500 ml) precooled to -20° so that the temperature of the mixture was kept in the range -15° to -20°. The cooling bath was removed and the mixture was stirred at ca. -10° for 20 minutes. Water (1 liter) was added and the two-phase mixture was stirred for 30 minutes. The aqueous phase was extracted with dichloromethane (2×500 ml), and the organic phases were washed sequentially with 2N hydrochloric acid (1 liter), combined and evaporated to a brown gum. The gum was dissolved in methanol (3.6 liters) and this solution was stirred and treated with saturated aqueous sodium hydrogen carbonate solution (1.2 liters) over a period of 10 minutes. The mixture was stirred at ca. 20° for 1.5 hours and a small quantity of brown solid was removed by filtration. The yellow filtrate was concentrated in vacuo (bath temp. not greater than 40°) to ca. 1.5 liters and water (1.5 liters) was added. The resulting suspension was refrigerated for 1 hour, and the yellow solid was filtered off, washed well with water, sucked as dry as possible and dried in vacuo at 40° for 24 hours. The greasy solid thus obtained, followed by toluene-p-sulphonic acid monohydrate (81 g, 0.425 mole), were added to stirred chloroform (2 liters). After several minutes the toluene-p-sulphonic acid salt began to crystallise. Stirring was continued for a further 30 minutes, after which the water was removed azeotropically in vacuo with continuous replacement of the chloroform so as to maintain a volume of 2 liters. The suspension was refrigerated overnight and the product was filtered off, slurry washed with chloroform (2×250 ml), refiltered, washed by displacement with chloroform (250 ml) and dried in vacuo at 40° to give the title compound as an off-white crystalline solid (237.8 g, 74.1%); λmax (EtOH) 262 nm (ε 7,250); the NMR spectrum (Me2SO-d6) indicated the presence of 0.25 mole of chloroform.

Provenance & Evidence