Ethyl Acetate → Cefuroxime Axetil

Participants

Reaction Steps

(RS)-1-Acetoxyethylbromide (12.5 g) was added to a stirred mixture of sodium cefuroxime (20 g) in dimethyl acetamide (110 ml) at 0° C. The mixture was stirred at +1° for 90 minutes and potassium carbonate (0.5 g) was added. Stirring was continued for a further 2 hours at 1-3° when the reaction mixture was added to a rapidly stirred mixture of ethyl acetate (200 ml) and aqueous 3% sodium bicarbonate (200 ml) to destroy any excess 1-acetoxyethylbromide. After 1 hour the organic layer (1.5% Δ2 isomer by HPLC) was separated, washed with N hydrochloric acid (100 ml) and aqueous 20% sodium chloride containing 2% sodium bicarbonate (30 ml). All three aqueous phases were sequentially washed with ethyl acetate (100 ml). The combined organic extracts were stirred for 30 minutes with charcoal (Norit SX Plus; 2g), filtered through a kieselguhr bed which was washed with ethyl acetate (2×25 ml). The combined filtrate and washes were evaporated in vacuo to 150 g and stirred at ambient temperature for 1 hour until the crystallisation was well established. Di-isopropyl ether (250 ml) was added over 45 minutes to complete the crystallisation and stirring was continued for an additional 1 hour. The product was collected by filtration, washed with 2:1 diisopropyl ether/ethyl acetate (150 ml) and dried for a weekend in vacuo at 50° to give crystalline cefuroxime axetil (19.3 g).

Provenance & Evidence