Benzimidazole → HCID 5328451, compound

HRID 545296Notes

Reaction equation

HRID 545296 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1.[H-].[Na+].F[C:13]1[CH:22]=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][CH:14]=1>CN(C=O)C.O>[N:1]1([C:13]2[CH:22]=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][CH:14]=2)[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1

Participants

6

Reactant 3

HCID 5798BenzimidazoleHCID 24758Sodium hydrideHCID 67878Methyl 4-fluorobenzoate

Product 1

HCID 5328451HCID 5328451, compoundYield 76%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (2.3 g, 19.46 mmol) 1H-benzimidazole in DMF (80 mL) at 0° C. was added sodium hydride (0.78 g, 19.46 mol, 60 wt. %) and the reaction mixture was stirred at 0° C. for 30 minutes, then at room temperature for 1 hour. Methyl 4-fluorobenzoate (3.0 g, 19.46 mmol) was then added and the reaction mixture was heated at 85° C. for 24 h. The reaction mixture was cooled to room temperature, diluted with water (300 mL) and extracted with dichloromethane (4×250 mL). The combined organic layers were washed with water (2×250 mL), saturated aqueous sodium chloride (200 mL), dried (magnesium sulfate) and the solvent removed in vacuo to give a crude oil. Purification by flash column chromatography (silica, ethyl acetate:hexanes 2:10) provided 3.7 g (76%) of methyl 4-(1H-benzimidazol-1-yl)benzoate as a white solid. To a solution of methyl 4-(1H-benzimidazol-1-yl)benzoate (3.7 g, 14.7 mmol) dissolved in THF/MeOH (1:1, 90 mL) was added 1.0 M aqueous NaOH (0.587 g, 14.67 mmol) and the reaction mixture was allowed to stir for 12 h at room temperature and the solvent removed in vacuo. The residue was diluted with water (100 mL), cooled to 0° C., and the pH was adjusted to 6.0 with 1.0 N aqueous HCl. The resulting precipitate was filtered and dried to afford 3.4 g (96%) of 4-(1H-benzimidazol-1-yl)benzoic acid as a white solid. MS [239.0 m/e (M+H)].

Workup

  1. waitat room temperature for 1 hour
  2. temperaturethe reaction mixture was heated at 85° C. for 24 h
  3. temperatureThe reaction mixture was cooled to room temperature
  4. extractionextracted with dichloromethane (4×250 mL)
  5. washThe combined organic layers were washed with water (2×250 mL), saturated aqueous sodium chloride (200 mL)
  6. dry with materialdried (magnesium sulfate)
  7. customthe solvent removed in vacuo
  8. customto give a crude oil
  9. customPurification by flash column chromatography (silica, ethyl acetate:hexanes 2:10)

Sources & evidence

ORD record
ord-4b0848ac0f43452fb5f7a5d52856ddf8
Source dataset
uspto-grants-2011_05
Patent number
US07935719B2

Reaction notes

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