4-Bromobenzaldehyde → 2'-TrifluoroMethyl-Biphenyl-4-Carbaldehyde

HRID 1669242Notes

Reaction equation

HRID 1669242 reaction equation
Br[C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.B(O)(O)[C:11]1[C:16]([C:17]([F:20])([F:19])[F:18])=[CH:15][CH:14]=[CH:13][CH:12]=1.[F-].[K+]>C1COCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1>[F:18][C:17]([F:20])([F:19])[C:16]1[CH:11]=[CH:12][CH:13]=[CH:14][C:15]=1[C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 707414-BromobenzaldehydeHCID 522689Potassium FluorideHCID 27343872-(Trifluoromethyl)benzeneboronic acid

Product 1

HCID 13926532'-TrifluoroMethyl-Biphenyl-4-CarbaldehydeYield 78.1%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 27342162-(Dicyclohexylphosphino)biphenylCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-bromobenzaldehyde (1 g, 5.40 mmol) in THF (21.6 mL) is added (2-trifluoromethyl)phenylboronic acid (1.67 g, 8.1 mmol), potassium fluoride (780 mg, 16.2 mmol), palladium(II) acetate (12.1 mg, 0.054 mmol), and 2-(dicyclohexylphosphino)-biphenyl (37.9 mg, 0.108 mmol). The reaction mixture is heated to reflux overnight. After cooling to rt, the reaction mixture is partitioned between dichloromethane and water. The aqueous layer is back-extracted with dichloromethane, the combined organic layers are dried and concentrated, then loaded onto silica gel and eluted using hexanes with an ethyl acetate gradient from 0% to 60% giving 2′-trifluoromethylbiphenyl-4-carbaldehyde (1.0548 g).

Workup

  1. temperatureThe reaction mixture is heated
  2. temperatureto reflux overnight
  3. customthe reaction mixture is partitioned between dichloromethane and water
  4. extractionThe aqueous layer is back-extracted with dichloromethane
  5. customthe combined organic layers are dried
  6. concentrationconcentrated
  7. washeluted

Sources & evidence

ORD record
ord-3076514e25ce44ba8c2ddb473812e79f
Source dataset
uspto-grants-2011_08
Patent number
US07989457B2

Reaction notes

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