4-Chlorophenol → (E)-5-[2-(4-chlorophenoxy)styryl]-8-fluoro-2,3-dihydro-1-methyl-1H-1,4-benzodiazepine dihydrochloride

Participants

Reaction Conditions

Reaction Steps

To a mixture of 56 mg (0.45 mmol) of 2-fluorobenzaldehyde and 64 mg (50 mmol) of 4-chlorophenol in 2.5 ml of dimethylformamide was added 75 mg (0.54 mmol) of sodium hydrogen carbonate. The mixture was heated at 95° C. for 18 hours. To the mixture at ambient temperature was added 118 mg (0.36 mmol) of (8-fluoro-1-methyl-1,2,3,4-tetrahydrobenzo[e][1,4]diazepin-5-ylidenemethyl)phosphonic acid diethyl ester followed by 25 mg (0.63 mmol) of sodium hydride (60% dispersion in mineral oil). The mixture was stirred for 2 hours. The mixture was partitioned between 12 ml of water and 3×4 ml of dichloromethane. The combined organic portions were dried (magnesium sulphate), filtered and evaporated. The product was purified by column chromatography (20 g IST pre-packed column) eluting with ethyl acetate and treated with 0.15 ml of 4M hydrogen chloride in dioxan. The solvent was evaporated to leave a red gum which was recrystallised from acetone/ethyl acetate/diethyl ether to give 17 mg of (E)-5-[2-(4-chlorophenoxy)styryl]-8-fluoro-2,3-dihydro-1-methyl-1H-1,4-benzodiazepine dihydrochloride as a red solid; MS: m/e 452 (M+).

Provenance & Evidence