Potassium Carbonate → 4'-(Trifluoromethyl)-4-biphenylcarbaldehyde

HRID 1669226Notes

Reaction equation

HRID 1669226 reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[CH:5][CH:4]=1.Br[C:15]1[CH:22]=[CH:21][C:18]([CH:19]=[O:20])=[CH:17][CH:16]=1.C(=O)([O-])[O-].[K+].[K+].CCOC(C)=O.CCCCCC>O1CCOCC1.O.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:1][C:2]([F:13])([F:12])[C:3]1[CH:8]=[CH:7][C:6]([C:15]2[CH:22]=[CH:21][C:18]([CH:19]=[O:20])=[CH:17][CH:16]=2)=[CH:5][CH:4]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 707414-BromobenzaldehydeHCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 21226206Ethyl acetate hexane

Product 1

HCID 27827124'-(Trifluoromethyl)-4-biphenylcarbaldehydeYield 99.7%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 167845palladium(II) acetateCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
70 °C

Procedure

To an ambient temperature solution of 4-(trifluoromethyl)phenylboronic acid (4.64 g, 24.43 mmol) in dioxane/water (15/15 mL) is added 4-bromo-benzaldehyde (4.42 g, 22.21 mmol), tetrabutylammonium bromide (7.16 g, 22.21 mmol, potassium carbonate (7.67 g, 55.53 mmol) and is degassed for 10 min. Palladium(II) acetate (748 mg, 1.11 mmol) is added and the reaction mixture is heated to 70° C. After 2 h TLC (20% EtOAc/hexane) indicates complete consumption of starting material. The reaction is cooled to room temperature diluted with water and extracted with EtOAc (3×200 mL). The combined organic extracts are washed with brine, dried (MgSO4), filtered, concentrated and chromatographed (330 g SiO2, 5% EtOAc/Hexanes) to yield the title compound (5.54 g, 94%). 1NMR (400 MHz, CDCl3) δ ppm: 10.09 (s, 1H), 8.01-8.00 (m, 1H), 7.99-7.98 (m, 1H), 7.78-7.75 (m, 2H), 7.74 (s, 4H).

Workup

  1. customis degassed for 10 min
  2. customconsumption of starting material
  3. temperatureThe reaction is cooled to room temperature
  4. additiondiluted with water
  5. extractionextracted with EtOAc (3×200 mL)
  6. washThe combined organic extracts are washed with brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customchromatographed (330 g SiO2, 5% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-22336d3f57154448b05863b0ce5f7201
Source dataset
uspto-grants-2011_08
Patent number
US07989457B2

Reaction notes

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