Sodium Carbonate → 6-Cyclopropyl-2,4'-difluoro-3-isopropoxybiphenyl-4-carbaldehyde

HRID 531100Notes

Reaction equation

HRID 531100 reaction equation
[CH:1]1(B(O)O)[CH2:3][CH2:2]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.C(=O)([O-])[O-].[Na+].[Na+].Br[C:43]1[C:48]([C:49]2[CH:54]=[CH:53][C:52]([F:55])=[CH:51][CH:50]=2)=[C:47]([F:56])[C:46]([O:57][CH:58]([CH3:60])[CH3:59])=[C:45]([CH:61]=[O:62])[CH:44]=1>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]>[CH:1]1([C:43]2[C:48]([C:49]3[CH:50]=[CH:51][C:52]([F:55])=[CH:53][CH:54]=3)=[C:47]([F:56])[C:46]([O:57][CH:58]([CH3:60])[CH3:59])=[C:45]([CH:61]=[O:62])[CH:44]=2)[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 2760897Cyclopropylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 1179922366-Bromo-2,4'-difluoro-3-isopropoxybiphenyl-4-carbaldehyde

Product 1

HCID 1179921726-Cyclopropyl-2,4'-difluoro-3-isopropoxybiphenyl-4-carbaldehydeYield 97.7%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

Cyclopropylboronic acid (13.8 g), dicyclohexyl(2′,6′-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine (6.58 g), tris(dibenzylideneacetone)dipalladium (0) (7.34 g) and 2M aqueous sodium carbonate solution (120 mL) were added to a solution of 6-bromo-2,4′-difluoro-3-isopropoxybiphenyl-4-carbaldehyde (28.5 g) in toluene (250 mL) at room temperature. The mixture was stirred at 100° C. under argon atmosphere for 16 hours. The mixture was filtrated through celite. The filtrate was extracted with ethyl acetate. The organic layer was separated, washed with water and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was purified by a silica gel column chromatography (hexane/ethyl acetate) to give the title compound (24.8 g).

Workup

  1. filtrationThe mixture was filtrated through celite
  2. extractionThe filtrate was extracted with ethyl acetate
  3. customThe organic layer was separated
  4. washwashed with water and brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by a silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-62cd7822122940a0b51302df5158d1a4
Source dataset
uspto-grants-2016_05
Patent number
US09353108B2

Reaction notes

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