Trifluoroacetic acid → 2,2,2-Trifluoro-1-(3'-fluorobiphenyl-4-yl)ethanol

HRID 254774Notes

Reaction equation

HRID 254774 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([Mg]Br)[CH:5]=[CH:6][CH:7]=1.Br[C:11]1[CH:16]=[CH:15][C:14]([CH:17]([OH:22])[C:18]([F:21])([F:20])[F:19])=[CH:13][CH:12]=1.C(O)(C(F)(F)F)=O>C1COCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:19][C:18]([F:20])([F:21])[CH:17]([C:14]1[CH:15]=[CH:16][C:11]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=2)=[CH:12][CH:13]=1)[OH:22]

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 112190241-(4-Bromophenyl)-2,2,2-trifluoroethanolHCID 178505773HCID 178505773, compound

Product 1

HCID 666495132,2,2-Trifluoro-1-(3'-fluorobiphenyl-4-yl)ethanolYield 94.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To Pd(PPh3)4 (2.1 g, 1.823 mmol) was added 3-fluorophenylmagnesium bromide (55 mls, 1.0 M in THF, 55 mmol) at 0° C. over 15 minutes. The ice bath was removed and the mixture was stirred for 30 minutes. 1-(4-Bromophenyl)-2,2,2-trifluoroethanol (4.65 g, 18.23 mmol) in THF (50 mls) was added over 10 minutes. The mixture was heated to reflux for 3 hours and was shown complete by LC (Sunfire column, TFA). The mixture was cooled, quenched with H2O, rotary evaporated to remove most of the THF, and extracted 3 times with CH2Cl2. The organics were combined washed with brine, dried over MgSO4, and concentrated. Chromatography (SiO2, CH2Cl2) gave 4.64 g of 2,2,2-trifluoro-1-(3′-fluorobiphenyl-4-yl)ethanol. Yield 94%.

Workup

  1. customThe ice bath was removed
  2. temperatureThe mixture was heated
  3. temperatureto reflux for 3 hours
  4. temperatureThe mixture was cooled
  5. customquenched with H2O
  6. customrotary evaporated
  7. customto remove most of the THF
  8. extractionextracted 3 times with CH2Cl2
  9. washThe organics were combined washed with brine
  10. dry with materialdried over MgSO4
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-4be693cade384cca878486affd7272c1
Source dataset
uspto-grants-2011_01
Patent number
US07875622B2

Reaction notes

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