Water → 4-bromo-2-(fluoromethyl)-1-(2-methyl-3-(trifluoromethyl)benzyl)-6-nitro-1H-benzo[d]imidazole

HRID 1622468Notes

Reaction equation

HRID 1622468 reaction equation
[Br:1][C:2]1[C:10]2[N:9]=[C:8]([CH2:11][F:12])[NH:7][C:6]=2[CH:5]=[C:4]([N+:13]([O-:15])=[O:14])[CH:3]=1.Br[CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[C:19]=1[CH3:28].C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[Br:1][C:2]1[C:10]2[N:9]=[C:8]([CH2:11][F:12])[N:7]([CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:25])([F:26])[F:27])[C:19]=3[CH3:28])[C:6]=2[CH:5]=[C:4]([N+:13]([O-:15])=[O:14])[CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 27756171-(Bromomethyl)-2-methyl-3-(trifluoromethyl)benzeneHCID 86687829HCID 86687829, compound

Product 1

HCID 866878304-bromo-2-(fluoromethyl)-1-(2-methyl-3-(trifluoromethyl)benzyl)-6-nitro-1H-benzo[d]imidazoleYield 62.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

Into a 250 ml of round bottom flask with 4-bromo-2-(fluoromethyl)-6-nitro-1H-benzo[d]imidazole (3 g, 10.95 mmol) in N,N-Dimethylformamide (DMF) (50 mL) was added 1-(bromomethyl)-2-methyl-3-(trifluoromethyl)benzene (4.16 g, 16.42 mmol) and potassium carbonate (4.54 g, 32.8 mmol). The resulting reaction mixture was stirred 1 h at 80° C., cooled to room temperature and poured into water, extracted with ethyl acetate, washed with water, brine, dried (MgSO4) and evaporated. The residue was purified on a silica gel cartridge and eluted with a gradient of 0% ethyl acetate/hexanes to 80% over 10 column volumes. The expected compound was collected and evaporated to yield 4-bromo-2-(fluoromethyl)-1-(2-methyl-3-(trifluoromethyl)benzyl)-6-nitro-1H-benzo[d]imidazole (3.05 g, 6.84 mmol, 62.4% yield) as a brown solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.56 (s, 3H) 5.54-5.78 (m, 4H) 6.51 (d, J=7.83 Hz, 1H) 7.18 (t, J=7.83 Hz, 1H) 7.64 (d, J=7.83 Hz, 1H) 8.13 (d, J=1.77 Hz, 1H) 8.44 (d, 1H); LC/MS: MS (ES+) m/e 447 [M+H]+.

Workup

  1. customThe resulting reaction mixture
  2. temperaturecooled to room temperature
  3. extractionextracted with ethyl acetate
  4. washwashed with water, brine
  5. dry with materialdried (MgSO4)
  6. customevaporated
  7. customThe residue was purified on a silica gel cartridge
  8. washeluted with a gradient of 0% ethyl acetate/hexanes to 80% over 10 column volumes
  9. customThe expected compound was collected
  10. customevaporated

Sources & evidence

ORD record
ord-17edc653b9a64091967fb60c185395a2
Source dataset
uspto-grants-2014_07
Patent number
US08778937B2

Reaction notes

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