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

HRID 841554Notes

Reaction equation

HRID 841554 reaction equation
[F:1][C:2]1[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[C:3]=1[CH2:4][N:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[C:13]([CH2:14]O)[C:8]=2[N:7]=[C:6]1[C:16]1[C:21]([F:22])=[CH:20][CH:19]=[CH:18][C:17]=1[F:23].O=S(Cl)[Cl:31]>C(Cl)(Cl)Cl>[F:1][C:2]1[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[C:3]=1[CH2:4][N:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[C:13]([CH2:14][Cl:31])[C:8]=2[N:7]=[C:6]1[C:16]1[C:21]([F:22])=[CH:20][CH:19]=[CH:18][C:17]=1[F:23]

Participants

4

Reactant 2

HCID 24386Thionyl ChlorideHCID 4926811-(2,6-Difluorobenzyl)-2-(2,6-difluorophenyl)-4-hydroxymethylbenzimidazole

Product 1

HCID 4926831-(2,6-Difluorobenzyl)-2-(2,6-difluorophenyl)-4-chloromethylbenzimidazoleYield 92%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Procedure

To 1-(2,6-difluorobenzyl)-2-(2,6-difluorophenyl)-4-hydroxylmethylbenzimidazole (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): δ7.55 (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).

Workup

  1. washwashed with NaHCO3 (sat. soln) and NaCl (sat. aq)
  2. dry with materialThe combined washings were dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe product was purified by flash chromatography
  6. washeluting with 1% MeOH/CH2Cl2
  7. customRecrystallization from diethylether:hexane (3:1)

Sources & evidence

ORD record
ord-8d37476b677d4f05b65dffe4aa9046b7
Source dataset
uspto-grants-2002_04
Patent number
US06369235B1

Reaction notes

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