Sodium Carbonate → 2-Cyclopropyl-4'-fluoro-5-methoxybiphenyl-4-carbaldehyde

HRID 531049Notes

Reaction equation

HRID 531049 reaction equation
Br[C:2]1[CH:7]=[C:6]([CH:8]=[O:9])[C:5]([O:10][CH3:11])=[CH:4][C:3]=1[C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=1.[CH:19]1(B(O)O)[CH2:21][CH2:20]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.C(=O)([O-])[O-].[Na+].[Na+]>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].O.C1(C)C=CC=CC=1>[CH:19]1([C:2]2[CH:7]=[C:6]([CH:8]=[O:9])[C:5]([O:10][CH3:11])=[CH:4][C:3]=2[C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)[CH2:21][CH2:20]1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 2760897Cyclopropylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 904235612-Bromo-4'-fluoro-5-methoxybiphenyl-4-carbaldehyde

Product 1

HCID 904228222-Cyclopropyl-4'-fluoro-5-methoxybiphenyl-4-carbaldehydeYield 53.9%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

2-Bromo-4′-fluoro-5-methoxybiphenyl-4-carbaldehyde (20.6 g), cyclopropylboronic acid (10.3 g), dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (4.10 g), tris(dibenzylideneacetone)dipalladium(0) (4.27 g), and a 2 M aqueous sodium carbonate solution (100 mL) were added to toluene (250 mL) in an argon atmosphere, and the mixture was stirred at 100° C. for 2 hours. The reaction mixture was allowed to cool to room temperature and poured to water, followed by extraction with ethyl acetate. The obtained organic layer was washed with saturated saline and dried over anhydrous magnesium sulfate, and then, the solvent was distilled off under reduced pressure. The obtained residue was passed through a short silica gel column (hexane/ethyl acetate), and then, the filtrate was concentrated. The residue was crystallized from a mixed solution of ethanol (50 mL) and water (10 mL), and the obtained crystals were washed with ethanol (85 mL) to obtain the title compound (9.70 g).

Workup

  1. temperatureto cool to room temperature
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe obtained organic layer was washed with saturated saline
  4. dry with materialdried over anhydrous magnesium sulfate
  5. distillationthe solvent was distilled off under reduced pressure
  6. concentrationthe filtrate was concentrated
  7. customThe residue was crystallized from a mixed solution of ethanol (50 mL) and water (10 mL)
  8. washthe obtained crystals were washed with ethanol (85 mL)

Sources & evidence

ORD record
ord-01cbbd1ea6f3462ebf5ee84cf76a9f36
Source dataset
uspto-grants-2016_05
Patent number
US09353108B2

Reaction notes

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