4-Methoxyphenol → 4-(3,5-Difluorophenoxy)anisole

HRID 1073523Notes

Reaction equation

HRID 1073523 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][CH:6]=1.[H][H].F[C:15]1[CH:20]=[C:19]([F:21])[CH:18]=[C:17]([F:22])[CH:16]=1>CCCCCC.CN(C)C=O>[F:22][C:17]1[CH:16]=[C:15]([CH:20]=[C:19]([F:21])[CH:18]=1)[O:11][C:8]1[CH:9]=[CH:10][C:5]([O:4][CH3:3])=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 90154-MethoxyphenolHCID 97451,3,5-TrifluorobenzeneHCID 24758Sodium hydrideHCID 178418361HCID 178418361, compound

Product 1

HCID 134559274-(3,5-Difluorophenoxy)anisoleYield 51.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8058HexaneSolvent

Procedure

Sodium hydride (7.56 g, 0.189 mol; 60% in oil) was washed with n-hexane to eliminate the oil, and N,N-dimethylformamide (100 ml) was added thereto to make a suspension. To the thus prepared suspension, 4-methoxyphenol (25.84 g, 0.208 mol) was gradually added with stirring, and stirring was continued until the generation of hydrogen gas ceased. 1,3,5-Trifluorobenzene (30.00 g, 0.227 mol) and cuprous chloride (0.50 g) were added thereto. The resultant mixture was heated under reflux for 8 hours with stirring. After allowed to cool, the reaction mixture was poured into ice-water and extracted with toluene. The toluene layer was dried over anhydrous magnesium sulfate. The solvent was removed, and the residual oil was distilled under reduced pressure to give 4-(3,5-difluorophenoxy)anisole (25.42 g). B.P., 98.5° C./0.2 mmHg.

Workup

  1. additionwas added
  2. stirringstirring
  3. temperatureunder reflux for 8 hours
  4. stirringwith stirring
  5. temperatureto cool
  6. extractionextracted with toluene
  7. dry with materialThe toluene layer was dried over anhydrous magnesium sulfate
  8. customThe solvent was removed
  9. distillationthe residual oil was distilled under reduced pressure

Sources & evidence

ORD record
ord-d25541a12b7a43858d57bf371d36b8a9
Source dataset
uspto-grants-1990_11
Patent number
US04970222

Reaction notes

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