反应详情

To 2-(2,6-difluorophenyl)-4-methoxylbenzimidazole (5005, Example 46) (0.28 g, 1.08 mmol) and 3,3-dimethylallyl bromide (0.20 mL, 0.26 mmol, 160 M %) dissolved in THF (3 mL) was added NaH (60% dispersion in mineral oil) (0.15 g, 3.75 mmol, 350 M %). After 4 h, the reaction was quenched with MeOH and concentrated. The residue was redissolved in dichloromethane, washed with water and NaCl (sat. aq.), dried (Na2SO4), filtered and concentrated. The product was purified by flash chromatography eluting with 2% MeOH/CH2Cl2 and recrystallized from hexane to give white powders of 1-(3,3-dimethylallyl)-2-(2,6-difluorophenyl)-4-methoxyl-benzimidazole (0.30 g, 0.91 mmol, 84% yield). M.p. 101-103° C. 1H-NMR (200 MHz, CD2Cl2): 7.52 (m, 1H, H4″), 7.24 (dd, J=7.9, 8.2 Hz, 1H, H6), 7.08 (m, 2H, H3″,5″), 7.02 (dd, J=0.9, 8.2 Hz, 1H, H5), 6.73 (dd, J=0.9, 7.9 Hz, 1H, H7), 5.19 (t, J=7.0 Hz, 1H, H2′), 4.02 (s, 3H, OCH3), 4.62 (d, J=7.0 Hz, 2H, H1′), 1.64 (s, 3H, CH3), 1.58 (s, 3H, CH3).

1. customthe reaction was quenched with MeOH
2. concentrationconcentrated
3. dissolutionThe residue was redissolved in dichloromethane
4. washwashed with water and NaCl (sat. aq.)
5. dry with materialdried (Na2SO4)
6. filtrationfiltered
7. concentrationconcentrated
8. customThe product was purified by flash chromatography
9. washeluting with 2% MeOH/CH2Cl2
10. customrecrystallized from hexane