Methanol → 4-Phenoxy-2-(trifluoromethyl)benzenemethanol

HRID 1946398Notes

Reaction equation

HRID 1946398 reaction equation
[C:1]1([O:7][C:8]2[CH:16]=[CH:15][C:11]([C:12](O)=[O:13])=[C:10]([C:17]([F:20])([F:19])[F:18])[CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CO>C1COCC1>[C:1]1([O:7][C:8]2[CH:16]=[CH:15][C:11]([CH2:12][OH:13])=[C:10]([C:17]([F:18])([F:19])[F:20])[CH:9]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

4

Reactant 2

HCID 887MethanolHCID 59547997HCID 59547997, compound

Product 1

HCID 584388914-Phenoxy-2-(trifluoromethyl)benzenemethanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 4-(phenyloxy)-2-(trifluoromethyl)benzoic acid (for a preparation see Intermediate 35)(0.507 g, 1.80 mmol), in THF (40 ml), under nitrogen, was added borane-tetrahydrofuran complex (0.463 g, 5.39 mmol, Aldrich) carefully over about 2 min. The solution was stirred for 40 min at ambient temperature and then heated at gentle reflux for 20 h. To the mixture at ambient temperature was added methanol (10 ml) dropwise and then the solution was heated to reflux for 30 min. The solvent was evaporated in vacuo and the residue acidified with dilute aqueous HCl. The mixture was extracted with chloroform and the phases separated using a hydrophobic frit. The solvent was evaporated in vacuo to leave [4-(phenyloxy)-2-(trifluoromethyl)phenyl]methanol as a colourless oil (0.491 g). [4-(phenyloxy)-2-(trifluoromethyl)phenyl]methanol (0.491 g, 1.83 mmol) in dichloromethane (10 ml) under nitrogen was stirred and cooled to −5° C. A solution of phosphorus tribromide (0.173 ml, 1.831 mmol) in DCM (3.5 ml) was then added dropwise over about 10 min. The solution was then allowed to warm to room temperature and stirred for 4 h. A saturated solution of aqueous sodium bicarbonate (10 ml) was then added and the mixture stirred vigorously. The emulsion was further diluted with water and chloroform. The phases were separated using a hydrophobic frit. The aqueous phase was further extracted with chloroform. The combined organic extracts were dried (Na2SO4) and filtered. The filtrate was re-dried with (MgSO4), filtered and the solvent removed in vacuo to give 4-(bromomethyl)-3-(trifluoromethyl)phenyl ether as a colourless oil (0.518 g).

Workup

  1. temperatureheated
  2. temperatureat gentle reflux for 20 h
  3. temperaturethe solution was heated
  4. temperatureto reflux for 30 min
  5. customThe solvent was evaporated in vacuo
  6. extractionThe mixture was extracted with chloroform
  7. customthe phases separated
  8. customThe solvent was evaporated in vacuo

Sources & evidence

ORD record
ord-fc5efee4660a4a6e9a2006e36cca26e2
Source dataset
uspto-grants-2013_03
Patent number
US08399436B2

Reaction notes

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