Phenol → 2-Phenoxy-3-trifluoromethyl-anisole

HRID 1822327Notes

Reaction equation

HRID 1822327 reaction equation
F[C:2]1[C:7]([O:8][CH3:9])=[CH:6][CH:5]=[CH:4][C:3]=1[C:10]([F:13])([F:12])[F:11].[C:14]1([OH:20])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O>[O:20]([C:2]1[C:3]([C:10]([F:13])([F:12])[F:11])=[CH:4][CH:5]=[CH:6][C:7]=1[O:8][CH3:9])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

5

Reactant 3

HCID 996PhenolHCID 11430Potassium CarbonateHCID 27747682-Fluoro-1-methoxy-3-(trifluoromethyl)benzene

Product 1

HCID 690761002-Phenoxy-3-trifluoromethyl-anisoleYield 53%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 2-fluoro-3-methoxybenzotrifluoride (4.76 g, 24.5 mmol), phenol (2.30 g, 24.4 mmol) and 325 mesh potassium carbonate (4.07 g, 29.4 mmol) in dry DMSO (50 mL) is heated to 130° C. and stirred 17 hours under N2. The reaction filtered to remove the solids, and the filtrate is acidified with 1 N HCl. The mixture is then diluted with water and extracted with Et2O. The organic layer is dried (Na2SO4) and the solvent is removed in vacuo to afford crude product that is absorbed on silica gel and purified by flash chromatography using 12/1 hexanes/ethyl acetate to afford 3.47 g (53%) of 2-phenoxy-3-trifluoromethyl-anisole (Rf=0.30 (4/1 hexanes/EtOAc) that is contaminated with starting 2-fluoro-1-methoxy-3-trifluoromethyl-benzene.

Workup

  1. filtrationThe reaction filtered
  2. customto remove the solids
  3. additionThe mixture is then diluted with water
  4. extractionextracted with Et2O
  5. dry with materialThe organic layer is dried (Na2SO4)
  6. customthe solvent is removed in vacuo
  7. customto afford crude product that
  8. customis absorbed on silica gel
  9. custompurified by flash chromatography

Sources & evidence

ORD record
ord-326347f9d7c24688a96f2c9a8ef4c32a
Source dataset
uspto-grants-2009_10
Patent number
US07608639B2

Reaction notes

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