Benzyl Alcohol → 1-(4-Benzyloxy-3-trifluoromethyl-phenyl)-ethanone

HRID 920525Notes

Reaction equation

HRID 920525 reaction equation
[CH2:1]([OH:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC([O-])(C)C.[K+].F[C:16]1[CH:21]=[CH:20][C:19]([C:22](=[O:24])[CH3:23])=[CH:18][C:17]=1[C:25]([F:28])([F:27])[F:26]>C1COCC1>[CH2:1]([O:8][C:16]1[CH:21]=[CH:20][C:19]([C:22](=[O:24])[CH3:23])=[CH:18][C:17]=1[C:25]([F:26])([F:27])[F:28])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 244Benzyl AlcoholHCID 6056784'-Fluoro-3'-(trifluoromethyl)acetophenoneHCID 23665647Potassium tert-butoxide

Product 1

HCID 670324791-(4-Benzyloxy-3-trifluoromethyl-phenyl)-ethanoneYield 72.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of benzyl alcohol (10.9 mL; 104.98 mmol) and KOtBu (12.96 g; 115.5 mmol) in THF (500 mL) was heated under reflux for 10 minutes. Subsequently, 4′-fluoro-3′-(trifluoromethyl)acetophenone (21.64 g; 105 mmol) was added and the mixture heated under reflux for another 2 hours. After cooling to RT, the mixture was partitioned between EtOAc and a 5% aqueous NaHCO3 solution. The organic layer was separated, dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by column chromatography (SiO2, Et2O:hexanes 1:2.5) to afford 1-(4-Benzyloxy-3-trifluoromethyl-phenyl)-ethanone (22.37 g).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 10 minutes
  3. temperaturethe mixture heated
  4. temperatureunder reflux for another 2 hours
  5. customthe mixture was partitioned between EtOAc
  6. customThe organic layer was separated
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by column chromatography (SiO2, Et2O:hexanes 1:2.5)

Sources & evidence

ORD record
ord-1d2a2c2718ca41aeaea2d02bd99b3327
Source dataset
uspto-grants-2016_03
Patent number
US09273017B2

Reaction notes

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