2-Fluorophenol → 2-[4-(2-Fluorophenoxy)phenyl]propionic acid

HRID 65592

Reaction equation

HRID 65592 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[OH:8].[OH-].[K+].I[C:12]1[CH:17]=[CH:16][C:15]([CH:18]([CH3:22])[C:19]([OH:21])=[O:20])=[CH:14][CH:13]=1>O.[Cu]>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[O:8][C:12]1[CH:17]=[CH:16][C:15]([CH:18]([CH3:22])[C:19]([OH:21])=[O:20])=[CH:14][CH:13]=1

Participants

6

Reactant 3

HCID 97072-FluorophenolHCID 14797Potassium HydroxideHCID 152255732-(4-Iodophenyl)propanoic acid

Product 1

HCID 205597862-[4-(2-Fluorophenoxy)phenyl]propionic acid

Reagents, catalysts & solvents 2

HCID 962WaterCatalystHCID 23978CopperCatalyst

Conditions

Temperature
180 °C

Procedure

2-Fluorophenol (2.35 g.) was fused with potassium hydroxide (1.7 g.) and a few drops of water by heating to 180° C. 2-(4-Iodophenyl)propionic acid (2.76 g.) and copper powder (0.1 g.) were then added and the melt ws heated at 160°-170° C. for 1 hour. The cooled solid was partitioned with methylene chloride (50 ml.) and 2.5N sodium hydroxide (50 ml.). The aqueous layer was acidified with hydrochloric acid, the resulting gum was extracted into ether, and the ether extract was extracted with saturated potassium carbonate solution. This aqueous extract was acidified with hydrochloric acid and the product isolated in ether. After evaporation the resulting solid was purified by preparative layer chromatography using 5% acetic acid/petroleum ether b.p. 62°-68° C. and eluting with ethyl acetate. Recrystallization from petroleum ether b.p. 62°-68° C. gave 2-[4-(2-fluorophenoxy)phenyl]propionic acid, m.p. 106°-108° C.

Workup

  1. temperaturethe melt ws heated at 160°-170° C. for 1 hour
  2. customThe cooled solid was partitioned with methylene chloride (50 ml.) and 2.5N sodium hydroxide (50 ml.)
  3. extractionthe resulting gum was extracted into ether
  4. extractionthe ether extract
  5. extractionwas extracted with saturated potassium carbonate solution
  6. extractionThis aqueous extract
  7. customthe product isolated in ether
  8. customAfter evaporation the resulting solid
  9. customwas purified by preparative layer chromatography
  10. washeluting with ethyl acetate
  11. customRecrystallization from petroleum ether b.p. 62°-68° C.

Sources & evidence

ORD record
ord-a480ab6c73eb43689a2bfa1d299ef1ed
Source dataset
uspto-grants-1978_12
Patent number
US04128573

Linked notes

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