Acetamide → 2-Bromo-5,6-dichloro-1-(5-deoxy-2,3-di-O-acetyl-beta-D-ribofuranosyl)benzimidazole

Participants

Reaction Steps

2-Bromo-5,6-dichloro-1H-benzimidazole (5.11 g, 19.21 mmol), and N,O-bis(trimethylsiyl) acetamide (Aldrich, 4.81 mL, 19.21 mmol) were combined with acetonitrile (Aldrich Sure Seal, 100 mL) and refluxed under nitrogen for 3 h. The solution was cooled to rt and trimethylsilyl triflate (Aldrich, 7.70 mL, 38.42 mmol) was added. After 15 min, 5-deoxy-1,2,3-tri-O-acetyl-D-ribofuranose (5.0 g, 19.21 mmol) in acetonitrile (4 mL) was added. The solution was stirred under nitrogen at rt for 3.5 h, then poured into 10% aqueous sodium bicarbonate (300 mL) and extracted with ethyl acetate (3×100 mL). The organic layers were washed with water (1×100 mL), dried with magnesium sulfate (anhyd), filtered, and evaporated. The crude residue was purified on a silica gel column with 1:30 acetone:CH2Cl2 to give the title compound (6.96 g, 14.93 mmol, 78%); MS (El): m/z (rel. intensity) 489 (0.22, M++Na); 1H NMR (DMSO-d6) δ8.13 (s, 1H, Ar—H), 8.02 (s, 1H, Ar—H), 6.17 (d, 1H, CH, J=6.6 Hz), 5.67 (t, 1H, CH, J=13.9 Hz), 5.29 (t, 1H, CH, J=7.2 Hz), 4.28 (m, 1H, CH), 2.16 (s, 3H, OAc), 2.04 (s, 3H, OAc), 1.53 (d, 3H, CH3, J=6.5 Hz).

Provenance & Evidence