Bromoacetonitrile → HCID 22394537, compound

Participants

Reaction Steps

4-(4-Benzo[1,3]dioxol-5-yl-5-pyridin-2-yl-1H-imidazol-2-yl)-phenol (357 mg; 1 mmol) was dissolved in tetrahydrofuran (20 ml) under argon and treated portionwise with sodium hydride (60% dispersion in oil; 60 mg; 1.5 mmol). When effervescence had ceased, bromoacetonitrile (178.5 mg; 103.5 μl ; 1.5 mmol) was added and the mixture was stirred at ambient temperature for 18 h. Saturated aqueous ammonium chloride solution was added and the nitrile extracted into ethyl acetate. The organic extracts were combined, washed with water, saturated brine, dried (MgSO4) and evaporated to dryness under reduced pressure. The residue was purified by chromatography through SiO2, eluting with ethyl acetate in 60-80° petroleum ether (50→100% ethyl acetate gradient), to give [4-(4-benzo[1,3]dioxol-5-yl-5-pyridin-2-yl-1H-imidazol-2-yl)-phenoxy]-acetonitrile (120 mg; 30%). This nitrile (120 mg; 0.31 mmol) was treated with ethanol (30 ml) and 2M aq. sodium hydroxide solution and the resulting mixture heated at reflux for 3 h. Cooled and evaporated to dryness under reduced pressure. The residue was treated with water and acidified to pH4-5 with 5M hydrochloric acid. The yellow precipitate was collected by filtration, washed with water and dried at 40° C. under reduced pressure (92 mg; 73%). 1H NMR (250 MHz; CD3OD) δ: 4.77 (2H, s), 6.12 (2H, s), 7.02 (1H, d), 7.12-7.14 (2H, m), 7.18 (2H, d), 7.44-7.49 (1H, m), 7.60 (1H, d), 7.86-7.92 (1H, m), 8.05 (2H, d), 8.72 (1H, d); m/z (API): 416.3 [M+H]⊕.

Provenance & Evidence