Isopropanol → 2,3',5'-Trifluoro[1,1'-biphenyl]-4-ol

HRID 444654Notes

Reaction equation

HRID 444654 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[F:9].[F:10][C:11]1[CH:12]=[C:13](B(O)O)[CH:14]=[C:15]([F:17])[CH:16]=1.C(=O)([O-])[O-].[K+].[K+].CC(O)C>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1(C)C=CC=CC=1.O>[OH:8][C:5]1[CH:6]=[CH:7][C:2]([C:13]2[CH:12]=[C:11]([F:10])[CH:16]=[C:15]([F:17])[CH:14]=2)=[C:3]([F:9])[CH:4]=1

Participants

8

Reactant 4

HCID 3776IsopropanolHCID 11430Potassium CarbonateHCID 2734338(3,5-Difluorophenyl)boronic acidHCID 27791534-Bromo-3-fluorophenol

Product 1

HCID 532193752,3',5'-Trifluoro[1,1'-biphenyl]-4-olYield 74%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
25 °C

Procedure

4-Bromo-3-fluorophenol (T-1) (50.0 g), 3,5-difluorophenylboronic acid (45.5 g), potassium carbonate (72.4 g), Pd(Ph3P)2Cl2 (5.52 g) and 2-propanol (500 ml) were put in a reaction vessel and heated to reflux for 5 hours under an atmosphere of nitrogen. After the reaction solution had been cooled to 25° C., it was poured into water (500 ml) and mixed with it. Toluene (500 ml) was added to the solution to separate organic and aqueous phases, and extraction was carried out. The combined organic phase was washed with water and dried over anhydrous magnesium sulfate. The resulting solution was concentrated under reduced pressure and the residue was purified with a fractional operation by means of column chromatography (silica gel; toluene). The product was further purified by recrystallization from a mixed solvent of heptane/Solmix A-11 and dried, giving 4-hydroxy-2,3′,5′-trifluoro-1,1′-biphenyl (T-2) (43.4 g). The yield based on the compound (T-1) was 74%.

Workup

  1. temperatureheated
  2. temperatureto reflux for 5 hours under an atmosphere of nitrogen
  3. additionmixed with it
  4. customto separate organic
  5. extractionaqueous phases, and extraction
  6. washThe combined organic phase was washed with water
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationThe resulting solution was concentrated under reduced pressure
  9. customthe residue was purified with a fractional operation by means of column chromatography (silica gel; toluene)
  10. customThe product was further purified by recrystallization from a mixed solvent of heptane/Solmix A-11
  11. customdried

Sources & evidence

ORD record
ord-f6431f45bf2b4cfe8d41b1b94bcf3602
Source dataset
uspto-grants-2013_07
Patent number
US08475888B2

Reaction notes

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