Sodium Carbonate → 6-Cyclopropyl-3-ethoxy-2,4'-difluorobiphenyl-4-carbaldehyde

HRID 531087Notes

Reaction equation

HRID 531087 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][CH2:58][CH3:59])=[C:45]([CH:60]=[O:61])[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][CH2:58][CH3:59])=[C:45]([CH:60]=[O:61])[CH:44]=2)[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 2760897Cyclopropylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 904237546-Bromo-3-ethoxy-2,4'-difluorobiphenyl-4-carbaldehyde

Product 1

HCID 904235146-Cyclopropyl-3-ethoxy-2,4'-difluorobiphenyl-4-carbaldehydeYield 95%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

Cyclopropylboronic acid (1.79 g), dicyclohexyl(2′,6′-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine (854 mg), tris(dibenzylideneacetone)dipalladium (0) (953 mg) and 2M aqueous sodium carbonate solution (15.6 mL) were added to a solution of 6-bromo-3-ethoxy-2,4′-difluorobiphenyl-4-carbaldehyde (3.55 g) in toluene (35 mL) at room temperature. The mixture was stirred at 100° C. under argon atmosphere for 16 hours. The mixture was quenched with water at room temperature and 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 (2.99 g).

Workup

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

Sources & evidence

ORD record
ord-4b348eac2ead450b83ed48b3067391ac
Source dataset
uspto-grants-2016_05
Patent number
US09353108B2

Reaction notes

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