Imidazole → 3-Fluoro-5-(1H-imidazol-1-yl)benzoic acid

HRID 431861Notes

Reaction equation

HRID 431861 reaction equation
Br[C:2]1[CH:7]=[C:6](F)[CH:5]=[C:4]([F:9])[CH:3]=1.[NH:10]1[CH:14]=[CH:13][N:12]=[CH:11]1.[C:15]([O-])([O-:17])=[O:16].[K+].[K+].O>CN(C=O)C>[F:9][C:4]1[CH:5]=[C:6]([CH:7]=[C:2]([N:10]2[CH:14]=[CH:13][N:12]=[CH:11]2)[CH:3]=1)[C:15]([OH:17])=[O:16]

Participants

6

Reactant 4

HCID 795ImidazoleHCID 962WaterHCID 11430Potassium CarbonateHCID 1363131-Bromo-3,5-difluorobenzene

Product 1

HCID 219424903-Fluoro-5-(1H-imidazol-1-yl)benzoic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1-Bromo-3,5-difluorobenzene (1.00 g, 5.18 mmol) was dissolved in anhydrous DMF (10 mL). The solution was chilled in an ice bath. Imidazole (0.36 g, 5.18 mmol) and K2CO3 (0.72 g, 5.18 mmol) were added. The reaction mixture was stirred at room temperature for 16 hours, and at 80° C. for 24 hours. The reaction mixture was poured into water (100 mL) and extracted with EtOAc. The organic phase was washed with brine, dried (MgSO4), filtered, and concentrated. The intermediate 3-Fluoro-5-Bromo-(1H-imidazol-1-yl)-benzene was used directly in the next step. Using the standard cyanation procedure, 3-Fluoro-5-cyano-(1H-imidazol-1-yl)-benzene was prepared as a colourless solid. The crude product was used directly in the next step. Using the standard saponification procedure, the title compound was prepared as a colourless solid. The crude product was used directly in the next step.

Workup

  1. temperatureThe solution was chilled in an ice bath
  2. waitat 80° C. for 24 hours
  3. extractionextracted with EtOAc
  4. washThe organic phase was washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customwas prepared as a colourless solid

Sources & evidence

ORD record
ord-159ddf544c28451da431092f56f10bfc
Source dataset
uspto-grants-2003_12
Patent number
US06660753B2

Reaction notes

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