Water → 1-(2,6-Difluorobenzyl)-2-(2,6-difluorophenyl)-4-hydroxymethylbenzimidazole

HRID 841552Notes

Reaction equation

HRID 841552 reaction equation
[F:1][C:2]1[CH:30]=[CH:29][CH:28]=[C:27]([F:31])[C:3]=1[CH2:4][N:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[C:13]([CH2:14][O:15]C(=O)C)[C:8]=2[N:7]=[C:6]1[C:19]1[C:24]([F:25])=[CH:23][CH:22]=[CH:21][C:20]=1[F:26].O.C([O-])([O-])=O.[K+].[K+]>CO>[F:1][C:2]1[CH:30]=[CH:29][CH:28]=[C:27]([F:31])[C:3]=1[CH2:4][N:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[C:13]([CH2:14][OH:15])[C:8]=2[N:7]=[C:6]1[C:19]1[C:20]([F:26])=[CH:21][CH:22]=[CH:23][C:24]=1[F:25]

Participants

5

Reactant 3

HCID 962WaterHCID 11430Potassium CarbonateHCID 22482478HCID 22482478, compound

Product 1

HCID 4926811-(2,6-Difluorobenzyl)-2-(2,6-difluorophenyl)-4-hydroxymethylbenzimidazoleYield 96%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To 1-(2,6-difluorobenzyl)-2-(2,6-difluorophenyl)-4-acetoxymethylbenzimidazole (Example 103) (1.45 g, 3.38 mmol) dissolved in methanol (19 mL) and water (1.0 mL) was added K2CO3 (0.40 g). After 30 min. the reaction was concentrated, redissolved in EtOAc, and washed with NaHSO4 (10% soln) and NaCl (sat. aq). The combined washings were dried (Na2SO4), filtered, and concentrated. Recrystallization of the crude product from diethylether:hexane (3:1) yielded white crystals of 1-(2,6-Difluorobenzyl)-2-(2,6-difluorophenyl)-4-hydroxymethylbenzimidazole (1.25 g, 3.24 mmol, 96% yield). M.p. 157-158° C. 1H-NMR (300 MHz, CD2Cl2): δ7.54 (m, 1H, H4′), 7.43 (d, J=7.9 Hz, 1H, H7), 7.30-7.22 (m, 2H, H6,4″), 7.18 (d, J=7.5 Hz, 1H, H5), 7.09 (m, 2H, H3′,5′), 6.82 (m, 2H, H3″,5″), 5.37 (s, 2H, CH2PhF2), 5.06 (d, J=5.4 Hz, 2H, CH2O), 3.51 (t, J=5.4 Hz, 1H, OH).

Workup

  1. concentrationAfter 30 min. the reaction was concentrated
  2. dissolutionredissolved in EtOAc
  3. washwashed with NaHSO4 (10% soln) and NaCl (sat. aq)
  4. dry with materialThe combined washings were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customRecrystallization of the crude product from diethylether:hexane (3:1)

Sources & evidence

ORD record
ord-5fa2191dddcb4510a35937a3c87de598
Source dataset
uspto-grants-2002_04
Patent number
US06369235B1

Reaction notes

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