Phenylacetic Acid → N,N'-Dicyclohexylurea

Participants

Reaction Steps

A freshly prepared mixture of 26 mg of concentrated sulfuric acid in 2.5 ml of absolute pyridine (suspension of pyridinium sulfate) is added, at 20° C. and while stirring, to a solution of 1.1 g (0.0025 mol) of prednisolone 17-ethyl carbonate and 1.2 g (0.0088 mol) of phenylacetic acid (dried at about 50°-60° C. in vacuo over P2O5 for 5 h.) in 6 ml of absolute pyridine. After stirring for 15 min., 720 mg (0.0035 mol) of N,N'-dicyclohexylcarbodiimide are added. A crystalline precipitate of the N,N'-dicyclohexylurea which has been formed soon appears in the initially clear solution. Stirring is continued until TLC no longer detects starting material and detects the reaction product at RF =0.8 (as a rule, a reaction period of 16 hours; a longer reaction period, e.g. standing or stirring over the weekend, does not impair the reaction result). After this, 0.3 ml of acetic acid are added and the mixture is left to stand for a further 1 h. at 20° C. and then 24-48 h. in a deep-freeze (about -15° C.). The precipitated N,N'-dicyclohexylurea is filtered off and washed with cold pyridine (about -15° C.), and the filtrate is stirred into about 400 ml of a quarter-saturated aqueous solution of sodium chloride; about 5 ml of ethanol are added and the oily-crystalline precipitate is filtered off, washed several times with water and then taken up in about 20 ml of methylene chloride. After drying with sodium sulfate, the solvent is distilled off and the residue is crystallized by adding diethyl ether or diisopropyl ether. 1.1 g of prednisolone 17-ethyl carbonate 21-phenylacetate with a melting point of 179°-183° C. are obtained and can be recrystallized from tertbutanol/diethylether.

Provenance & Evidence