Sodium hydride → 1H-Benzimidazole, 2-(2,6-difluorophenyl)-1-((2,6-difluorophenyl)methyl)-

HRID 841527

Reaction equation

HRID 841527 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[NH:10][C:11]2[CH:17]=[CH:16][CH:15]=[CH:14][C:12]=2[N:13]=1.[F:18][C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([F:25])[C:20]=1[C:26]1C=CC=CC=1CBr.[H-].[Na+]>C1COCC1>[F:18][C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([F:25])[C:20]=1[CH2:26][N:13]1[C:12]2[CH:14]=[CH:15][CH:16]=[CH:17][C:11]=2[N:10]=[C:9]1[C:3]1[C:4]([F:8])=[CH:5][CH:6]=[CH:7][C:2]=1[F:1]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 16536142-(2,6-difluorophenyl)-1H-benzimidazoleHCID 867579372,6-Difluorophenyl-alpha-bromotoluene

Product 1

HCID 4688471H-Benzimidazole, 2-(2,6-difluorophenyl)-1-((2,6-difluorophenyl)methyl)-Yield 85%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-d7caf3fa62a04a1baef3411b14d33c7a
Source dataset
uspto-grants-2002_04
Patent number
US06369235B1

Linked notes

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