Trichloroacetyl isocyanate → Cefuroxime Sodium

Participants

Reaction Steps

A mixture of THF (60 ml), dichloromethane (25 ml), and trichloroacetyl isocyanate (6.2 ml) was protected from moisture and cooled to -10°.To the stirred mixture was added (6R,7R)-7-[Z-2-(fur-2-yl)-2-methyoxyiminoacetamido]-3-hydroxymethylceph-3-em-4-carboxylic acid (10 g) in one charge followed by THF (20 ml). The mixture was stirred for 10 minutes at 0° to +5° to give a clear solution. Methanol (6.6 ml) was added, followed by portionwise addition of anhydrous sodium acetate (0.3 g) to raise the pH to 3.5. Charcoal (1 g) and filter aid (0.5 g Hyflo Supercel) were added and the mixture stirred at 10° for 20 minutes. Further anhydrous sodium acetate (5 g) was then added and the mixture stirred at 10° to 15° for 5 minutes by which time the pH had risen to 7.2. The charcoal, undissolved sodium acetate, and filter aid were removed by filtration and the filter bed washed with methanol (23 ml ) containing dichloromethane (10 ml). The filtrate and washes were combined, warmed to 25°, and left undisturbed at that temperature. Crystallisation commenced after 12 minutes. After 1 hour the mixture was stirred briefly and then left undisturbed for a further 11/2 hours. The crystalline material was collected by filtration, washed with THF (2×50 ml) and dried in vacuo at 35° to give sodium cefuroxime in a yield of 78.5%theory corrected for THF and sodium acetate.

Provenance & Evidence