反应详情

To 1-(2,6-difluorobenzyl)-2-(2,6-difluorophenyl)-4-methoxylbenzimidazole (Example 46) (0.30 g, 0.78 mmol) and hexadecyltrimethylammonium bromide (0.30 g) dissolved in acetic acid (9.0 mL) was added HBr (1.0 mL). After refluxing for 7 h, the reaction was concentrated. The residue was then diluted with EtOAc, and washed with NaHCO3 (sat. aq) and NaCl (sat. aq). The combined washing were dried (Na2SO4), filtered, and concentrated. The crude product was purified by flash chromatography eluting with 2% methanol/CH2Cl2 and recrystallization from diethylether, yielding 1-(2,6-Difluorobenzyl)-2-(2,6-difluorophenyl)-4-hydroxyl-benzimidazole (0.25 g, 0.67 mmol, 86% yield). M.p. 257-259° C. 1H NMR (200 MHz, CD2Cl2): δ 7.57 (m, 1H, H4′), 7.25 (m, 1H, H4″), 7.17 (dd, J=7.9, 8.3 Hz, 1H, H6), 7.12 (m, 2H, H3′,5′), 6.99 (d, J=8.3 Hz, 1H, H7), 6.82 (m, 2H, H3″,5″), 6.73 (dd, J=7.9, 1.0 Hz, H5), 5.35 (s, 2H, CH2PhF2).

1. temperatureAfter refluxing for 7 h
2. concentrationthe reaction was concentrated
3. additionThe residue was then diluted with EtOAc
4. washwashed with NaHCO3 (sat. aq) and NaCl (sat. aq)
5. washThe combined washing
6. dry with materialwere dried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated
9. customThe crude product was purified by flash chromatography
10. washeluting with 2% methanol/CH2Cl2 and recrystallization from diethylether