Pyridine → 4-Fluoro-2-(4-fluorophenoxy)benzoic acid

HRID 1293216Notes

Reaction equation

HRID 1293216 reaction equation
Cl[C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[F:12][C:13]1[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=1.C(=O)([O-])[O-].[K+].[K+].N1C=CC=CC=1>O.[Cu].[Cu]I>[F:11][C:9]1[CH:8]=[CH:7][C:3]([C:4]([OH:6])=[O:5])=[C:2]([O:19][C:16]2[CH:17]=[CH:18][C:13]([F:12])=[CH:14][CH:15]=2)[CH:10]=1

Participants

8

Reactant 4

HCID 1049PyridineHCID 97324-FluorophenolHCID 11430Potassium CarbonateHCID 752592-Chloro-4-fluorobenzoic acid

Product 1

HCID 575723224-Fluoro-2-(4-fluorophenoxy)benzoic acidYield 99%

Reagents, catalysts & solvents 3

HCID 23978CopperCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolvent2×

Procedure

A mixture of 2-chloro-4-fluorobenzoic acid (1.74 g, 10 mmol), 4-fluorophenol (2.24 g, 20 mmol), copper (50 mg, 0.78 mmol), copper(I) iodide (50 mg, 0.28 mmol), potassium carbonate (2.76 g, 20 mmol), and pyridine (0.40 mL, 5.0 mmol) in water (6.0 mL) was heated under reflux for 2 h with stirring. The reaction mixture was diluted with water and filtered through a pad of Celite®. The pH value of the filtrate was adjusted to 9.0 by the addition of 2 M aqueous solution of sodium carbonate. The aqueous mixture was extracted with dichloromethane (50 mL×3). The combined organic extracts were washed with brine (50 mL), dried (sodium sulfate), and concentrated to afford 29 mg (99%) of the title compound: MS (ESI) m/z 250 (M+).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 2 h
  3. filtrationfiltered through a pad of Celite®
  4. additionThe pH value of the filtrate was adjusted to 9.0 by the addition of 2 M aqueous solution of sodium carbonate
  5. extractionThe aqueous mixture was extracted with dichloromethane (50 mL×3)
  6. washThe combined organic extracts were washed with brine (50 mL)
  7. dry with materialdried (sodium sulfate)
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-02ebffe29e03487a850520a20f042869
Source dataset
uspto-grants-2007_07
Patent number
US07238714B2

Reaction notes

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