Water → 2-Cyclopropyl-5-ethoxy-2',4'-difluorobiphenyl-4-carbaldehyde

HRID 531143Notes

Reaction equation

HRID 531143 reaction equation
Br[C:2]1[CH:7]=[C:6]([CH:8]=[O:9])[C:5]([O:10][CH2:11][CH3:12])=[CH:4][C:3]=1[C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=1[F:20].[CH:21]1(B(O)O)[CH2:23][CH2:22]1.C(=O)([O-])[O-].[Na+].[Na+].O>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>[CH:21]1([C:2]2[CH:7]=[C:6]([CH:8]=[O:9])[C:5]([O:10][CH2:11][CH3:12])=[CH:4][C:3]=2[C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=2[F:20])[CH2:23][CH2:22]1

Participants

8

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 2760897Cyclopropylboronic acidHCID 1179923172-Bromo-5-ethoxy-2',4'-difluorobiphenyl-4-carbaldehyde

Product 1

HCID 1179923862-Cyclopropyl-5-ethoxy-2',4'-difluorobiphenyl-4-carbaldehydeYield 91.5%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2-bromo-5-ethoxy-2′,4′-difluorobiphenyl-4-carbaldehyde (5.70 g), cyclopropylboronic acid (2.15 g), dicyclohexyl(2′,6′-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine (549 mg), tris(dibenzylideneacetone)dipalladium (0) (612 mg) and 2 M aqueous sodium carbonate solution (25.1 mL) in toluene (50 mL) was stirred at 100° C. for 2 hours under nitrogen atmosphere. The mixture was poured into water at room temperature and extracted with ethyl acetate. The organic layer was separated, washed with brine, dried over anhydrous magnesium sulfate. Activated carbon (600 mg) was added to the filtrate. The mixture was stirred for 20 minutes at room temperature. After filtration, the filtrate was concentrated in vacuo. The residue was purified by a silica gel column chromatography (hexane/ethyl acetate) to give the title compound (4.62 g).

Workup

  1. extractionextracted with ethyl acetate
  2. customThe organic layer was separated
  3. washwashed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. additionActivated carbon (600 mg) was added to the filtrate
  6. stirringThe mixture was stirred for 20 minutes at room temperature
  7. filtrationAfter filtration
  8. concentrationthe filtrate was concentrated in vacuo
  9. customThe residue was purified by a silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-0431033c8bac4c66859dbbb6e34170f0
Source dataset
uspto-grants-2016_05
Patent number
US09353108B2

Reaction notes

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