Potassium Phosphate, Tribasic → 4'-Fluoro-3-methoxy-[1,1'-biphenyl]-4-carbaldehyde

HRID 531047Notes

Reaction equation

HRID 531047 reaction equation
Br[C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[C:4]([O:10][CH3:11])[CH:3]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[F:20][C:21]1[CH:26]=[CH:25][C:24](B(O)O)=[CH:23][CH:22]=1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C1(C)C=CC=CC=1>[F:20][C:21]1[CH:26]=[CH:25][C:24]([C:2]2[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[C:4]([O:10][CH3:11])[CH:3]=2)=[CH:23][CH:22]=1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2856454-Fluorophenylboronic acidHCID 110530414-Bromo-2-methoxybenzaldehyde

Product 1

HCID 225667274'-Fluoro-3-methoxy-[1,1'-biphenyl]-4-carbaldehydeYield 59.8%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

Palladium acetate (2.61 g) was added to a mixture of 4-bromo-2-methoxybenzaldehyde (25.0 g), tripotassium phosphate (74.0 g), (4-fluorophenyl)boronic acid (24.4 g), tricyclohexylphosphine (20% toluene solution, 41.3 mL), toluene (250 mL), and water (125 mL), and the resultant mixture was stirred at 90° C. for 3 hours in an argon atmosphere. The reaction mixture was allowed to cool to room temperature, and then, the organic layer was separated. The aqueous layer was subjected to extraction with ethyl acetate. Combined organic layers were washed with water and saturated saline in this order and dried over anhydrous magnesium sulfate, and then, the solvent was distilled off under reduced pressure. The obtained residue was crystallized from methanol (150 mL) to obtain the title compound (16.0 g).

Workup

  1. customthe organic layer was separated
  2. extractionThe aqueous layer was subjected to extraction with ethyl acetate
  3. washCombined organic layers were washed with water and saturated saline in this order
  4. dry with materialdried over anhydrous magnesium sulfate
  5. distillationthe solvent was distilled off under reduced pressure
  6. customThe obtained residue was crystallized from methanol (150 mL)

Sources & evidence

ORD record
ord-9a78c1f836294f7d85f24f5a351b8ce9
Source dataset
uspto-grants-2016_05
Patent number
US09353108B2

Reaction notes

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