Dichloromethane → 1,1-dimethylethyl 7-[4-(1-{[(2-methylpropyl)oxy]carbonyl}-1H-imidazol-2-yl)phenyl]-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate

Participants

Reaction Conditions

Reaction Steps

A solution of isobutyl 2-(4-bromophenyl)-1H-imidazole-1-carboxylate (example 4, step 5) (0.50 g, 1.55 mmol), (4-{[(1,1-dimethylethyl)oxy]carbonyl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)boronic acid (example 1, step 2) (0.63 g, 1.70 mmol) and diisopropyethylamine (1.50 mL, 8.50 mmol) in 20% aqueous 1,4-dioxane (10 mL) was deoxygenated for five minutes by bubbling nitrogen gas into it, followed by the addition of 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium(II) complex with dichloromethane (70 mg, 0.085 mmol). The reaction mixture was heated to 80° C. for 2 hours. On cooling to room temperature the mixture was diluted with ethyl acetate (250 mL) then filtered through a pad of Celite. The organic filtrate was washed with 10% aqueous citric acid (50 mL), brine then dried over anhydrous sodium sulfate, filtered and concentrated. Silica gel column chromatography (hexane-ethyl acetate 9:1 to 7:3) provided 1,1-dimethylethyl 7-[4-(1-{[(2-methylpropyl)oxy]carbonyl}-1H-imidazol-2-yl)phenyl]-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (0.32 g. 43%). 1H NMR (400 MHz, d6-DMSO): 7.73 (d, 1H), 7.67 (s, 4H), 7.56 (m, 2H), 7.14 (d, 1H), 7.08 (m, 1H), 4.56 (br s, 1H), 4.51 (br s, 2H), 4.13 (br s, 1H), 4.08 (m, 2H), 3.74 (m, 2H), 1.86 (m, 1H), 1.34 (s, 1H), 1.32 (s, 9H), 0.77 (d, 6H). MS (EI) for C28H33N3O5: 492 (MH+).

Provenance & Evidence