Acetoacetic Acid → 2-Bromo-5,6-dichloro-1-(5-deoxy-beta-D-ribofuranosyl)-1H-benzimidazole

2-Bromo-5,6-dichloro-1-(2,3-di-O-acetyl-5deoxy-beta-D-ribofuranosyl)-1H-benzimidazole (7.70 g, 16.52 mmol) was dissolved in ethanol (100 mL) and methanol (100 mL). A solution of sodium carbonate (1.75 g, 16.52 mmol) in water (30 mL) was added to the diacetate solution. The resulting mixture was stirred at rt for 17 h. The reaction mixture was concentrated, dissolved in ethyl acetate (125 mL) and extracted with water (3×50 mL). The ethyl acetate layer was dried with magnesium sulfate (anhyd), filtered, and evaporated. The crude residue was purified on a silica gel column with 1:30 methanol:CH—2Cl2. The resulting product was further purified on a silica gel column with 1:2 ethyl acetate: hexanes, followed by 1:1 ethyl acetate:hexanes to give the title compound (3.00 g, 7.85 mmol, 48%); MS (El): m/z (rel. intensity) 405 (0.05, M++Na); 1H NMR (DMSO-d6) δ8.00 (s, 1H, Ar—H), 7.87 (s, 1H, Ar—H), 5.87 (d, 1H, OH, J=6.7 Hz), 5.53 (d, 1H, OH, J=6.2 Hz), 5.29 (d, 1H, CH, J=5.1 Hz), 4.52 (m, 1H, CH), 4.01 (m, 1H, CH), 3.91 (m, 1H, CH), 1.42 (d, 3H, CH3, J=6.5 Hz).

1. concentrationThe reaction mixture was concentrated
2. dissolutiondissolved in ethyl acetate (125 mL)
3. extractionextracted with water (3×50 mL)
4. dry with materialThe ethyl acetate layer was dried with magnesium sulfate (anhyd)
5. filtrationfiltered
6. customevaporated
7. customThe crude residue was purified on a silica gel column with 1:30 methanol
8. customThe resulting product was further purified on a silica gel column with 1:2 ethyl acetate

ORD record

ord-93139f25358c4f18b48c226fd94ad7df

Source dataset

uspto-grants-2002_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06413938B1