Hydrochloric Acid → Cefuroxime

Participants

Reaction Steps

Dichlorophosphinyl isocyanate (1.46 ml) was added to a stirred suspension of (6R,7R)-7-[Z-2-(fur-2-yl)-2-methoxyiminoacetamido]-3-hydroxymethylceph-3-em-4-carboxylic acid (3.81 g) in acetonitrile (50 ml) cooled to 5°. The reaction mixture was stirred at 5° for 15 minutes and then added to a solution of NaHCO3 (5.1 g) in water (100 ml). This mixture was stirred for 10 minutes when the pH was adjusted from 7.4 to 5.0 with hydrochloric acid. The pH fell to 3.0 after a further 10 minutes so it was readjusted to 5.0 with aqueous sodium hydroxide solution. The mixture was kept at ca. 20° overnight and then heated at 45° for 2 hours when TLC (chloroform:methanol:acetic acid=9:2:1) showed that reaction was essentially complete. The precipitated white solid was removed by filtration and the filtrate was washed with ethyl acetate. The aqueous phase was acidified to pH 1.9 with dilute hydrochloric acid in the presence of ethyl acetate. The aqueous phase was re-extracted with ethyl acetate, and the combined ethyl acetate extracts were washed with 25% aqueous sodium chloride solution and then evaporated. The solid residue was triturated with diethyl ether to give the title compound (3.18 g, 75.0%), purity by HPLC 95.4% and by TLC 91%.

Provenance & Evidence