Nordiazepam → 7-chloro-1,3-dihydro-1-(2,2-dimethoxyethyl)-5-phenyl-2H-1,4-benzodiazepine-2-one

Participants

Reaction Steps

To a solution of 27.1 g. (0.1 mole) of 7-chloro-1,3 -dihydro-5-phenyl-2H-1,4-benzodiazepine-2-one in 300 ml. of dry dimethylformamide was added 4.6 g. (0.11 mole) of 57% sodium hydride in mineral oil, under nitrogen and with continuous stirring. After stirring one hour at room temperature, 25.4 g. (0.15 mol) of redistilled bromoacetaldehyde dimethylacetal in 10 ml. of dimethylformamide was added and the reaction mixture is kept at 100° C. with stirring during 16 hours. The mixture was then concentrated in vacuo to one-half the volume, well shaken with ice water and extracted with methylene chloride. The extract was washed with water, dried over Na2SO4 and evaporated at 25° C. and 0.2 mm.Hg pressure giving a brown oil which was crystallized from 2-propanol yielding 26.2 g. (73% of light brown crystals m.p. 115-117° C. A sample chromatographed on silica gel, eluted with 2% methanol-98% chloroform, evaporated in vacuo, and crystallized from 2-propanol gave 7-chloro -1,3-dihydro-1-(2,2-dimethoxyethyl)-5-phenyl-2H-1,4 -benzodiazepine-2-one of melting point 117° to 119° C.

Provenance & Evidence