反应详情

2-(2,6-difluorophenyl)benzimidazole (Example 12) (2.00 g, 8.70 mmol) and 2,6-difluoro-α-bromo-toluene (25) (2.85 g, 160 M%), were dissolved in THF (20 mL). To this mixture, NaH (0.75 g, 215 M%) was added. After mixing for 2 hours, the reaction was quenched with MeOH and concentrated. The residue was redissolved in ethylacetate, and washed with NaHCO3 (sat. aq.) and NaCl (sat. aq.). The combined washings were dried (Na2SO4), filtered and concentrated. The crude product was recrystallized from ethylacetate/hexane (1:1) yielding white powders of 1-(2,6-difluorobenzyl)-2-(2,6-difluorophenyl)benzimidazole (2.62 g, 0.35 mmol, 85% yield. M.p. 145° C. 1H-NMR (300 MHz, CD2Cl2): δ7.77 (m, 1H, H4), 7.54 (m, 1H, H4′), 7.49m, 1H, H7), 7.29 (m, 2H, H5,6), 7.24 (m, 1H, H4″), 7.08 (m, 2H, H3′,5′), 5.82 (m, 2H, H3″,5″), 5.30 (s, 2H, CH2PhF2).

1. additionAfter mixing for 2 hours
2. customthe reaction was quenched with MeOH
3. concentrationconcentrated
4. dissolutionThe residue was redissolved in ethylacetate
5. washwashed with NaHCO3 (sat. aq.) and NaCl (sat. aq.)
6. dry with materialThe combined washings were dried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated
9. customThe crude product was recrystallized from ethylacetate/hexane (1:1)