Methanol → [2-Bromo-6-(trifluoromethoxy)phenyl]methanol

HRID 1946417Notes

Reaction equation

HRID 1946417 reaction equation
[Br:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][C:12]([F:15])([F:14])[F:13])[C:3]=1[C:4](O)=[O:5].CO>C1COCC1>[Br:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][C:12]([F:14])([F:13])[F:15])[C:3]=1[CH2:4][OH:5]

Participants

4

Reactant 2

HCID 887MethanolHCID 111088792-Bromo-6-(trifluoromethoxy)benzoic acid

Product 1

HCID 66770602[2-Bromo-6-(trifluoromethoxy)phenyl]methanolYield 100.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 2-bromo-6-[(trifluoromethyl)oxy]benzoic acid (1.116 g, 3.92 mmol, Parkway Scientific), in THF (45 ml), under nitrogen, was added 1.0 M borane-tetrahydrofuran complex (12 ml, 12 mmol) carefully over about 2 minutes. The solution was then heated at gentle reflux for 24 h and allowed to cool. Methanol (20 ml) was added dropwise. The solution was heated at reflux for 30 min and allowed to cool. The solvent was evaporated in vacuo and acidified with dilute aqueous HCl. The mixture was extracted with chloroform and then filtered through a hydrophobic frit. The chloroform was evaporated in vacuo to give {2-bromo-6-[(trifluoromethyl)oxy]phenyl}methanol as a colourless oil (1.07 g). {2-bromo-6-[(trifluoromethyl)oxy]phenyl}methanol (1.06 g, 3.91 mmol) in dichloromethane (14 ml) under nitrogen was stirred and cooled to −10° C. A solution of phosphorus tribromide (0.37 ml, 3.91 mmol) in DCM (3.5 ml) was then added dropwise over about 12 min. The temperature was allowed to rise to ambient temperature over about 3 h then stirred for a further 2 h. Saturated aqueous sodium bicarbonate (12 ml) was then added in portions with stirring and the mixture left in a fridge over weekend. The mixture was extracted into chloroform three times. The combined chloroform extracts were filtered through a hydrophobic frit and the solvent was evaporated in vacuo to give 1-bromo-2-(bromomethyl)-3-[(trifluoromethyl)oxy]benzene as a colourless oil (0.6 g).

Workup

  1. temperatureThe solution was then heated
  2. temperatureat gentle reflux for 24 h
  3. temperatureto cool
  4. temperatureThe solution was heated
  5. temperatureat reflux for 30 min
  6. temperatureto cool
  7. customThe solvent was evaporated in vacuo
  8. extractionThe mixture was extracted with chloroform
  9. filtrationfiltered through a hydrophobic frit
  10. customThe chloroform was evaporated in vacuo

Sources & evidence

ORD record
ord-23cc6ad03ff5426ea5dc73628bb6a759
Source dataset
uspto-grants-2013_03
Patent number
US08399436B2

Reaction notes

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