Benzimidazole, 5,6-dimethyl-2-trifluoromethyl- → HCID 15376227, compound

HRID 2256398Notes

Reaction equation

HRID 2256398 reaction equation
[CH3:1][C:2]1[C:14]([CH3:15])=[CH:13][C:5]2[NH:6][C:7]([C:9]([F:12])([F:11])[F:10])=[N:8][C:4]=2[CH:3]=1.[H-].[Na+].[CH3:18][O:19][C:20](=[O:29])[C:21]1[CH:26]=[CH:25][C:24]([CH2:27]Br)=[CH:23][CH:22]=1>CN(C=O)C>[CH3:18][O:19][C:20](=[O:29])[C:21]1[CH:26]=[CH:25][C:24]([CH2:27][N:8]2[C:4]3[CH:3]=[C:2]([CH3:1])[C:14]([CH3:15])=[CH:13][C:5]=3[N:6]=[C:7]2[C:9]([F:12])([F:10])[F:11])=[CH:23][CH:22]=1

Participants

5

Reactant 3

HCID 15725Benzimidazole, 5,6-dimethyl-2-trifluoromethyl-HCID 24758Sodium hydrideHCID 256687Methyl 4-(bromomethyl)benzoate

Product 1

HCID 15376227HCID 15376227, compoundYield 23.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5,6-Dimethyl-2-trifluoromethyl-1H-benzoimidazole (2.14 g, 0.01 mol) was dissolved in DMF (50 mL). Sodium hydride (60% dispersion in oil, 0.48 g, 0.012 mol) was added and the reaction mixture was stirred at ambient temperature for 0.5 hour under an atmosphere of nitrogen. 4-Bromomethyl benzoic acid methyl ester (2.29 g, 0.01 mol) was then added. The mixture was stirred at 80° C. for 18 hours. Most of the solvent was evaporated. The residue was diluted with water and extracted with ethyl acetate. The organic phase was washed with water, dried over anhydrous sodium sulfate then evaporated. The residue was crystallized from ethyl acetate/hexane twice to afford pure title compound (0.85 g, 23.5% yield) as a white solid, m.p. 150°-152° C. Anal. Calcd. for C19H17F3N2O2 : C, 62.98; H, 4.73; N, 7.73. Found: C, 62.96; H, 4.73; N, 7.56. Mass spectrum (+FAB; [M+H]+) 363. 1H-NMR (DMSO-d6 ; 400 MHz) δ 7.90 (d, 1H), 7.63 (s, 1H), 7.45 (s, 1H), 7.15 (d, 2H), 5.74 (s, 2H), 3.81 (s, 3H), 2.33 (s, 3H), and 2.30 ppm (s, 3H).

Workup

  1. stirringThe mixture was stirred at 80° C. for 18 hours
  2. customMost of the solvent was evaporated
  3. additionThe residue was diluted with water
  4. extractionextracted with ethyl acetate
  5. washThe organic phase was washed with water
  6. dry with materialdried over anhydrous sodium sulfate
  7. customthen evaporated
  8. customThe residue was crystallized from ethyl acetate/hexane twice

Sources & evidence

ORD record
ord-5ae0fb11f64a4f349fa9a36f0daa11e7
Source dataset
uspto-grants-1997_08
Patent number
US05654436

Reaction notes

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