Diazepam → 7-chloro-1-methyl-5-phenyl-2-trimethylsiloxy-1H-1,4-benzodiazepine

Participants

Reaction Conditions

Reaction Steps

A solution of methyllithium in diethyl ether (0.0275 mol, 15.3 ml of 1.8 M solution) was added dropwise to a solution of 3.04 g (0.03 mol) of diisopropylamine in 25 ml of diethyl ether. The reaction mixture was cooled to -70° C. and a solution of 7.12 g (0.025 mol) of 7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one in 40 ml of tetrahydrofuran was added dropwise. The reaction mixture became dark red. Trimethylchlorosilane (11.4 ml; 0.09 mol) was added dropwise, after which the reaction mixture was warmed to room temperature, stirred for 3 hours and then filtered. The filtrate was evaporated to dryness and the residue was dissolved in 150 ml of trichlorofluoromethane. This solution was filtered to remove undissolved solid; the filtrate was evaporated to dryness under reduced pressure to give 8.52 g of 7-chloro-1-methyl-5-phenyl-2-trimethylsiloxy-1H-1,4-benzodiazepine as a light orange glass: 1H NMR (CCl3F) δ 0.0 ppm (s, 9H), 2.62 ppm (s, 3H), 5.76 ppm (s, 1H) and 6.4-7.6 ppm (m, 8H).

Provenance & Evidence