2-Fluorophenol → 4-(2-Fluorophenoxy)benzoic acid

HRID 2247687Notes

Reaction equation

HRID 2247687 reaction equation
F[C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.[F:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[OH:17].C(=O)([O-])[O-:19].[K+].[K+].CC(=CC)C.P([O-])(O)(O)=O.[K+].Cl[O-].[Na+]>CN(C)C=O.O>[F:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[O:17][C:2]1[CH:9]=[CH:8][C:5]([C:6]([OH:19])=[O:7])=[CH:4][CH:3]=1

Participants

9

Reactant 6

HCID 97072-FluorophenolHCID 105532-Methyl-2-buteneHCID 11430Potassium CarbonateHCID 680234-FluorobenzaldehydeHCID 516951Monobasic potassium phosphateHCID 23665760Sodium Hypochlorite

Product 1

HCID 200595614-(2-Fluorophenoxy)benzoic acidYield 87%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-fluorobenzaldehyde (1.2 g, 10 mmol) and 2-fluorophenol (1.3 g, 12 mmol) in N,N-dimethylformamide (10 ml) was added potassium carbonate (2.8 g, 20 mmol) with stirring, and the resulting mixture was stirred at 100° C. for 16 hours. After cooling to room temperature, the reaction mixture was poured into water (20 ml) and extracted with ether. The extract was washed with a saturated aqueous solution of sodium chloride and dried over magnesium sulfate. After filtration, the filtrate was evaporated in vacuo. Subsequently, to a solution of the residue obtained in a mixture of tetrahydrofuran (5 ml), t-butanol (10 ml), and water (5 ml) were added successively 2-methyl-2-butene (5.3 ml, 50 mmol), potassium dihydrogenphosphate (3.4 g, 25 mmol), and sodium hypochlorite (2.7 g, 30 mmol) with stirring, and the resulting mixture was stirred at room temperature for 2 hours. After stirring, the reaction mixture was poured into water (20 ml) and extracted with ether. Subsequently, to the aqueous layer was added a 1M aqueous sodium hydroxide solution (20 ml), and the resulting aqueous layer was acidified with a 10M aqueous hydrochloric acid solution (2 ml) and extracted again with ether. The extract was washed with a saturated aqueous solution of sodium chloride and dried over magnesium sulfate. After filtration, the filtrate was evaporated in vacuo to afford the title compound (2.0 g) in a yield of 87% as a white crystalline solid.

Workup

  1. stirringthe resulting mixture was stirred at 100° C. for 16 hours
  2. extractionextracted with ether
  3. washThe extract was washed with a saturated aqueous solution of sodium chloride
  4. dry with materialdried over magnesium sulfate
  5. filtrationAfter filtration
  6. customthe filtrate was evaporated in vacuo
  7. customSubsequently, to a solution of the residue obtained in a mixture of tetrahydrofuran (5 ml), t-butanol (10 ml), and water (5 ml)
  8. stirringwith stirring
  9. stirringthe resulting mixture was stirred at room temperature for 2 hours
  10. stirringAfter stirring
  11. extractionextracted with ether
  12. additionSubsequently, to the aqueous layer was added a 1M aqueous sodium hydroxide solution (20 ml)
  13. extractionextracted again with ether
  14. washThe extract was washed with a saturated aqueous solution of sodium chloride
  15. dry with materialdried over magnesium sulfate
  16. filtrationAfter filtration
  17. customthe filtrate was evaporated in vacuo

Sources & evidence

ORD record
ord-ff9489898eb242a898c70a6954bf98c0
Source dataset
uspto-grants-2010_03
Patent number
US07687491B2

Reaction notes

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