Ethyl bromoacetate → Ethyl [4-(2,2,2-trifluoro-1,1-dimethylethyl)phenoxy]acetate

HRID 1350815Notes

Reaction equation

HRID 1350815 reaction equation
[F:1][C:2]([F:14])([F:13])[C:3]([C:6]1[CH:11]=[CH:10][C:9]([OH:12])=[CH:8][CH:7]=1)([CH3:5])[CH3:4].C(=O)([O-])[O-].[K+].[K+].Br[CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24]>CN(C)C=O>[F:1][C:2]([F:13])([F:14])[C:3]([C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])=[CH:8][CH:7]=1)([CH3:5])[CH3:4]

Participants

5

Reactant 3

HCID 7748Ethyl bromoacetateHCID 11430Potassium CarbonateHCID 220907484-(1,1,1-Trifluoro-2-methylpropan-2-yl)phenol

Product 1

HCID 86604944Ethyl [4-(2,2,2-trifluoro-1,1-dimethylethyl)phenoxy]acetate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 4-(2,2,2-trifluoro-1,1-dimethylethyl)phenol (408 mg, 2.0 mmol, WO 9708144A1) and potassium carbonate (552 mg, 4.0 mmol) in N,N-dimethylformamide (DMF) (30 ml) was added ethyl bromoacetate (334 mg, 2.0 mmol) and the mixture was stirred for 3 hours at ambient temperature. The reaction was partitioned with water and a 1:10 by volume mixture of ethylacetate/hexane, and the organic layer was separated and dried over sodium sulfate. After filtration to separate solvent and sodium sulfate, the solvent was removed under reduced pressure to give a residue, which was passed through a silica gel chromatography column and eluted with a 1:1 by volume mixture of ethyl acetate/hexane to furnish ethyl [4-(2,2,2-trifluoro-1,1-dimethylethyl)phenoxy]acetate. Then, ethyl [4-(2,2,2-trifluoro-1,1-dimethylethyl)phenoxy]acetate was treated with 2M aqueous sodium hydroxide (3.0 ml) and methanol (3.0 ml) for 2 hours at room temperature and was quenched with 2M aqueous hydrogen chloride to acidify the mixture adjusting to pH 1. Crude product was extracted with ethyl acetate, and then the organic layer was dried over magnesium sulfate. After filtration, solvent was evaporated under reduced pressure to give 345 mg (66% yield) of the title compound as a white solid.

Workup

  1. customThe reaction was partitioned with water
  2. additiona 1:10 by volume mixture of ethylacetate/hexane
  3. customthe organic layer was separated
  4. dry with materialdried over sodium sulfate
  5. filtrationAfter filtration
  6. customto separate solvent and sodium sulfate
  7. customthe solvent was removed under reduced pressure
  8. customto give a residue, which
  9. washeluted with a 1:1 by volume mixture of ethyl acetate/hexane

Sources & evidence

ORD record
ord-51558433c72d47109338b181d0849f95
Source dataset
uspto-grants-2007_05
Patent number
US07214824B2

Reaction notes

Loading…