Sodium Hydroxide → 4-(1H-Benzimidazol-1-yl)benzoic acid

HRID 545297Notes

Reaction equation

HRID 545297 reaction equation
[N:1]1([C:10]2[CH:19]=[CH:18][C:13]([C:14]([O:16]C)=[O:15])=[CH:12][CH:11]=2)[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1.[OH-].[Na+]>C1COCC1.CO>[N:1]1([C:10]2[CH:19]=[CH:18][C:13]([C:14]([OH:16])=[O:15])=[CH:12][CH:11]=2)[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 5328451HCID 5328451, compound

Product 1

HCID 49621894-(1H-Benzimidazol-1-yl)benzoic acidYield 97.1%

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

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. customthe solvent removed in vacuo
  2. additionThe residue was diluted with water (100 mL)
  3. temperaturecooled to 0° C.
  4. filtrationThe resulting precipitate was filtered
  5. customdried

Sources & evidence

ORD record
ord-5bba88195035453f86cfad212bd8ccfc
Source dataset
uspto-grants-2011_05
Patent number
US07935719B2

Reaction notes

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