反应详情

温度

85 °C

5,6-Dichloro-1-(3-acetyl-2,5-dideoxy-2-fluoro-beta-D-ribofuranosyl)-1H-benzimidazole (0.45 g, 1.3 mmoles) was boiled in toluene to remove water. Excess toluene was removed in vacuo. THF (Aldrich, Sure Seal, 20 mL) was added and the solution heated to reflux in an 85° C. oil bath. NBS (Aldrich, 0.46 g, 2.6 mmoles, 2 eq.) was added and the reaction refluxed 7 mins. A second portion (0.23 g, 1.3 mmoles, 1 eq.) was added and reflux continued 10 mins. The reaction was removed from the heat, diluted with chloroform (40 mL) and cooled to room temperature. The solution was washed with sat. sodium bicarbonate (2×), dried with MgSO4 and filtered. The solvents were removed in vacuo and the residue purified by chromatography on 75 g of silica gel eluted with ethyl acetate/hexane (1:4, v/v). The product containing fractions were combined and the solvents removed in vacuo. The yield was 0.42 g, 75%. MS (FAB+): m/z, 425; 1H NMR (DMSO-d6) δ7.99 (s,1H, Ar—H), 7.97 (s, 1H, Ar—H), 6.27 (d, 1H, H-1′, J=19 Hz), 5.69 (d, 1H, H-2′, J=53 Hz), 5.1 (m, 1H), 4.25 (m, 1H), 2.13 (s, 3H, acetyl), 1.45 (d, 3H, H-5′, J=6 Hz).

1. customto remove water
2. customExcess toluene was removed in vacuo
3. additionTHF (Aldrich, Sure Seal, 20 mL) was added
4. temperaturethe solution heated
5. temperaturethe reaction refluxed 7 mins
6. additionA second portion (0.23 g, 1.3 mmoles, 1 eq.) was added
7. temperaturereflux
8. customThe reaction was removed from the heat
9. additiondiluted with chloroform (40 mL)
10. temperaturecooled to room temperature
11. washThe solution was washed with sat. sodium bicarbonate (2×)
12. dry with materialdried with MgSO4
13. filtrationfiltered
14. customThe solvents were removed in vacuo
15. customthe residue purified by chromatography on 75 g of silica gel
16. washeluted with ethyl acetate/hexane (1:4, v/v)
17. additionThe product containing fractions
18. customthe solvents removed in vacuo