Citric Acid → 1,1-dimethylethyl 7-[4-(1H-imidazol-2-yl)phenyl]-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate

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Reaction Conditions

Reaction Steps

1,1-Dimethylethyl 2-(4-bromophenyl)-1H-imidazole-1-carboxylate (457 mg, 1.41 mmol) and (4-{[(1,1-dimethylethyl)oxy]carbonyl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)boronic acid (example 1, step 2) (456 mg, 1.55 mmol) were taken into dioxane (5 mL) and water (1 mL) followed by addition of DIPEA (1.1 mL, 6.2 mmol) and dichloro[1,1-bis(diphenylphosphino]ferrocenepalladium (II) dichloromethane adduct (58 mg) then the mixture was heated at 80° C. over 12 h. The mixture was cooled then partitioned with ethyl acetate and 10% aqueous citric acid. The organic solution was washed with brine, dried over anhydrous sodium sulfate then filtered and concentrated. The residue thus obtained was taken into methanol (10 mL) followed by addition of sodium hydroxide (180 mg, 4.5 mmol) in water (1 mL). The mixture was stirred at room temperature for 30 minutes then neutralized by addition of 10% aqueous citric acid then concentrated. The aqueous residue was partitioned with ethyl acetate and saturated aqueous sodium bicarbonate and the organic solution was washed with brine, dried over anhydrous sodium sulfate then filtered and concentrated to give 1,1-dimethylethyl 7-[4-(1H-imidazol-2-yl)phenyl]-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (490 mg, 89% yield). MS (EI) for C23H25N3O3: 392 (MH+).

Provenance & Evidence