Thionyl Chloride → 1-(2,6-Difluorobenzyl)-2-(2,6-difluorophenyl)-4-chloromethylbenzimidazole

Participants

Reaction Steps

To 1-(2,6-difluorobenzyl)-2-(2,6-difluorophenyl)-4-hydroxylmethyl-benzimidazole (Example 112) (0.54 g, 1.40 mmol) dissolved in CHCl3 (3.0 mL) was added SOCl2 (0.15 mL, 2.06 mmol, 150 M %). After 3 h at room temperature, the reaction was diluted with CHCl3, and washed with NaHCO3 (sat. soln) and NaCl (sat. aq). The combined washings were dried (Na2SO4), filtered and concentrated. The product was purified by flash chromatography eluting with 1% MeOH/CH2Cl2. Recrystallization from diethylether:hexane (3:1) yielded white crystals of 1-(2,6-difluorobenzyl)-2-(2,6-difluorophenyl)-4-chloromethylbenzimidazole (0.52 g, 1.28 mmol, 92% yield). M.p. 143-144° C. 1H-NMR (300 MHz, CD2Cl2): δ 7.55 (m, 1H, H4′), 7.48 (dd, J=7.7, 1.1 Hz, 1H, H7), 7.36 (dd, J=7.6 Hz, 1.1 Hz, 1H, H5), 7.30 (dd, J=7.7, 7.6 Hz, 1H, H6), 7.25 (m, 1H, H4″), 7.09 (m, 2H, H3′,5′), 6.82 (m, 2H, H3″,5″), 5.36 (s, 2H, CH2PhF2), 5.07 (s, 2H, CH2Cl).

Provenance & Evidence