Sodium hydride → (S)-1-(m-chlorophenyl)-7-fluoro-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one

Participants

Reaction Steps

A suspension of 8.20 g (35 mmol) of (S)-7-fluoro-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11(10H)-dione in 40 ml of dry N,N-dimethylformamide is treated at -30° to -20° with 1.53 g (35 mmol) of sodium hydride (55 percent oil dispersion), the mixture is stirred at the above temperature for a further 35 minutes, and then at -60° there are added dropwise 7.25 ml (35 mmol) of phosphoric acid diphenyl ester chloride in 7 ml of dry N,N-dimethylformamide. The temperature is allowed to rise to -35°, the mixture is then again cooled to -70° and there is added a solution of 5.03 g (35 mmol) of 3-chlorobenzyl isocyanide in 5 ml of dry N,N-dimethylformamide, and subsequently there is added a solution of 3.92 g (35 mmol) of potassium t-butylate in 7 ml of dry N,N-dimethylformamide. After completion of the addition, the mixture is left to warm to 20°, neutralized by the addition of 1.5 ml of glacial acetic acid and poured into 250 ml of water. The mixture is extracted five times with methylene chloride, the combined organic extracts are washed three times with water, dried over magnesium sulfate, and evaporated. The residue is chromatographed on silica gel while eluting with ethyl acetate and recrystallized from ethyl acetate and n-hexane. There is obtained (S)-1-(m-chlorophenyl)-7-fluoro-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one having a melting point of 182°-183°.

Provenance & Evidence