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 twophase 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 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