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

HRID 1622481Notes

Reaction equation

HRID 1622481 reaction equation
CN(C=O)C.[Br:6][C:7]1[C:15]2[N:14]=[C:13]([CH:16]([F:18])[F:17])[NH:12][C:11]=2[CH:10]=[C:9]([N+:19]([O-:21])=[O:20])[CH:8]=1.Br[CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:33])([F:32])[F:31])[C:25]=1[CH3:34].C(=O)([O-])[O-].[K+].[K+]>O>[Br:6][C:7]1[C:15]2[N:14]=[C:13]([CH:16]([F:17])[F:18])[N:12]([CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:31])([F:32])[F:33])[C:25]=3[CH3:34])[C:11]=2[CH:10]=[C:9]([N+:19]([O-:21])=[O:20])[CH:8]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 27756171-(Bromomethyl)-2-methyl-3-(trifluoromethyl)benzeneHCID 866878364-bromo-2-(difluoromethyl)-6-nitro-1H-benzo[d]imidazole

Product 1

HCID 866878404-bromo-2-(difluoromethyl)-1-(2-methyl-3-(trifluoromethyl)benzyl)-6-nitro-1H-benzo[d]imidazoleYield 35%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a 100 mL round bottomed flask containing DMF (30 mL) was added 4-bromo-2-(difluoromethyl)-6-nitro-1H-benzo[d]imidazole (3.2 g, 10.96 mmol), 1-(bromomethyl)-2-methyl-3-(trifluoromethyl)benzene (1.60 mL, 9.48 mmol) and potassium carbonate (2.3 g, 16.64 mmol). The resultant suspension was heated to 65° C. and after stirring for 2 hrs the mixture was allowed to cool to rt and diluted with 35 mL H2O. The resulting slurry was extracted several times with EtOAc, the organic dried over Na2SO4 and concentrated to give a thick oil which was adsorbed onto a silical gel column and was eluted with EtOAc/Hex 10% to 20% gradient over 15 column volumes on a 25 g silica column. The fractions containing desired product were combined and concentrated desired product (1.54 g, 3.32 mmol, 30.3% yield) as a light orange powder. LC/MS: MS (ES+) m/e 464.2 [M+H]+; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.52 (d, J=1.77 Hz, 1H), 8.07 (d, J=2.02 Hz, 1H), 7.66 (d, J=7.83 Hz, 1H), 7.20 (d, J=3.79 Hz, 1H), 7.07 (s, 1H), 6.94 (s, 1H), 6.52 (d, J=8.08 Hz, 1H), 5.73 (s, 2H), 2.58 (s, 3H).

Workup

  1. extractionThe resulting slurry was extracted several times with EtOAc
  2. dry with materialthe organic dried over Na2SO4
  3. concentrationconcentrated
  4. customto give a thick oil which
  5. washwas eluted with EtOAc/Hex 10% to 20% gradient over 15 column volumes on a 25 g silica column
  6. additionThe fractions containing desired product

Sources & evidence

ORD record
ord-54dee65cd35845aa8c31469fbbbead6d
Source dataset
uspto-grants-2014_07
Patent number
US08778937B2

Reaction notes

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