Hydrochloric Acid → 1-[4-Hydroxy-2′-(trifluoromethyl)[1,1′-biphenyl]-3-yl]ethanone

HRID 1619654Notes

Reaction equation

HRID 1619654 reaction equation
[CH3:1][C:2]([C:4]1[CH:9]=[C:8](Br)[CH:7]=[CH:6][C:5]=1[OH:11])=[O:3].[F:12][C:13]([F:24])([F:23])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1B(O)O.C(=O)([O-])[O-].[K+].[K+].Cl>O1CCOCC1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[OH:11][C:5]1[CH:6]=[CH:7][C:8]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=2[C:13]([F:24])([F:23])[F:12])=[CH:9][C:4]=1[C:2](=[O:3])[CH3:1]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 959915'-Bromo-2'-hydroxyacetophenoneHCID 27343872-(Trifluoromethyl)benzeneboronic acid

Product 1

HCID 580423421-[4-Hydroxy-2′-(trifluoromethyl)[1,1′-biphenyl]-3-yl]ethanoneYield 95%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 5-bromo-2-hydroxy acetophenone (3.00 g, 13.9 mmol), 2-(trifluoromethyl)benzeneboronic acid (3.97 g, 20.9 mmol), potassium carbonate (3.86 g, 27.9 mmol) and tetrakistriphenylphosphinepalladium (0) (1.61 g, 1.39 mmol) in 1,4-dioxane (90 mL) and water (18.0 mL) was heated to 50° C. over 2 days under an atmosphere of nitrogen. The reaction was allowed to cool to room temperature and poured into a 1M aqueous solution of hydrogen chloride (50 mL). The aqueous layer was then extracted with ethyl acetate (3×50 mL). The combined organics were washed with water (50 mL), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to afford a brown oil. The oil was purified by silica gel column chromatography (10% ethyl acetate in heptane) to afford the title compound as a colourless oil (3.70 g, 95%).

Workup

  1. temperatureto cool to room temperature
  2. extractionThe aqueous layer was then extracted with ethyl acetate (3×50 mL)
  3. washThe combined organics were washed with water (50 mL)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto afford a brown oil
  8. customThe oil was purified by silica gel column chromatography (10% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-93c3ed6c583040989b5a2363ab569723
Source dataset
uspto-grants-2014_07
Patent number
US08772293B2

Reaction notes

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