Hydrogen Peroxide → 2-(2,6-Difluorophenyl)-1-[(2,6-difluorophenyl)methyl]benzimidazole-4-carboxamide

HRID 841550Notes

Reaction equation

HRID 841550 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]([C:14]#[N:15])[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].C([O-])([O-])=[O:30].[Na+].[Na+].OO>C(O)C>[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]([C:14]([NH2:15])=[O:30])[C:8]=2[N:7]=[C:6]1[C:16]1[C:17]([F:23])=[CH:18][CH:19]=[CH:20][C:21]=1[F:22]

Participants

5

Reactant 3

HCID 784Hydrogen PeroxideHCID 10340Sodium CarbonateHCID 98647011-(2,6-Difluorobenzyl)-2-(2,6-difluorophenyl)benzimidazole-4-carbonitrile

Product 1

HCID 4926802-(2,6-Difluorophenyl)-1-[(2,6-difluorophenyl)methyl]benzimidazole-4-carboxamideYield 72%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To 1-(2,6-Difluorobenzyl)-2-(2,6-difluorophenyl)benzimidazole-4-carbonitrile (Example 105) (1.10 g, 2.88 mmol) dissolved in ethanol (100 mL) and 3 M Na2CO3 (10 mL) was added 30% hydrogen peroxide (10 mL). After stirring overnight at room temperature, the reaction was concentrated. The residue was then redissolved in EtOAc, and washed with NaHSO4(10% soln), NaHCO3 (sat. aq) and NaCl (sat. aq). The combined washings were dried (Na2SO4), filtered and concentrated. The crude product was purified by flash chromatography eluting with 2% methanol/CH2Cl2 and recrystallization from methanol, yielding white crystals of 1-(2,6-difluorobenzyl)-2-(2,6-difluorophenyl)benzimidazole-4-carboxylic acid amide (0.83 g, 2.08 mmol, 72% yield). M.p. 260-261° C. 1H-NMR (200 MHz, CD2Cl2): δ8.10 (dd, J=1.1, 7.7 Hz, 1H, H5), 7.71 (br d, J=8.1 Hz, 1H, H7), 7.59 (m, 1H, H4′), 7.43 (dd, J=7.7, 8.1 Hz, 1H, H6), 7.28 (m, 1H, H4″), 7.13 (m, 2H, H3′,5′), 6.84 (m, 2H, H3″,5″), 5.43 (s, 2H) CH2PhF2), 1.92 (s, 2H, NH2).

Workup

  1. concentrationthe reaction was concentrated
  2. dissolutionThe residue was then redissolved in EtOAc
  3. washwashed with NaHSO4(10% soln), NaHCO3 (sat. aq) and NaCl (sat. aq)
  4. dry with materialThe combined washings were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by flash chromatography
  8. washeluting with 2% methanol/CH2Cl2 and recrystallization from methanol

Sources & evidence

ORD record
ord-2786cba7b59e48b1a671dbbe7c9893f4
Source dataset
uspto-grants-2002_04
Patent number
US06369235B1

Reaction notes

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