Dicyclohexylcarbodiimide → N,N'-Dicyclohexylurea

Participants

Reaction Steps

Bendamustine free base (1.0 g, 2.79 mmol) in dichloromethane (90 ml), morpholinoethanol (0.44 ml, 3.35 mmol) and DMAP (20 mg) were added with stirring. A solution of N,N′-Dicyclohexylcarbodiimide (0.63 g, 3.05 mmol) in dichloromethane (90 ml) was added dropwise over 50 min. After 15 min, a clear reaction solution was obtained and after 70 min a precipitate of dicyclohexyl urea occurred. The reaction mixture was stirred at ambient temperature for a total time of 24 h. After concentration to half of the volume and cooling to 0° C., the precipitate was removed by filtration. Then the solution was extracted with diluted HCl (1 ml 37% HCl to 60 ml Water, 30 ml+2×15 ml portions). The aqueous phase was treated with 25% NH3 (1.6 ml, pH 7-8) and extracted with dichloromethane (20+2×10 ml). Evaporation of the combined organic solvents resulted in a crude oil (1.38 g) that was purified via column chromatography (40 g silica, 10% MeOH/dichloromethane) to afford a slightly yellowish oil (1.26 g) that crystallized after seeding. Further drying in vacuum resulted in 1.08 g (82%) of product as slightly yellowish crystals.

Provenance & Evidence