Phosphorisocyanatidic dichloride → Cefuroxime

Participants

Reaction Steps

Dichlorophosphinyl isocyanate (1.46 ml,) was added to a solution of (6R,7R)-7-[Z-2-(fur-2-yl)-2-methoxyiminoacetamido]-3-hydroxymethylceph-3-em-4-carboxylic acid (3.81 g) in THF (50 ml) at 22°, the temperature rising to 31°. The reaction mixture was stirred for 15 minutes and then added to a solution of sodium acetate (5.72 g) in water (50 ml). More sodium acetate (1.64 g) was added over 10 minutes to give a stable pH of 4.6. This solution was stirred at 30° for 1 hour and then heated at 45° for 3.5 hours when TLC (as Example 3) showed the reaction to be complete. The solution, pH 4.6, was clarified by filtration, adjusted to pH 7.0 with aqueous NaHCO3 solution and washed twice with ethyl acetate. The aqueous phase was stirred and acidified to pH 1.9 with dilute hydrochloric acid to precipitate the title compound (2.80 g, 66.0%); purity by HPLC 95.8% and by TLC 96%.

Provenance & Evidence