Sodium Carbonate → 2,3,4'-Trifluorobiphenyl-4-carbaldehyde

HRID 531132Notes

Reaction equation

HRID 531132 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5](B(O)O)=[CH:4][CH:3]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.C(=O)([O-])[O-].[Na+].[Na+].Br[C:47]1[CH:54]=[CH:53][C:50]([CH:51]=[O:52])=[C:49]([F:55])[C:48]=1[F:56]>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>[F:56][C:48]1[C:49]([F:55])=[C:50]([CH:51]=[O:52])[CH:53]=[CH:54][C:47]=1[C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 269863904-Bromo-2,3-difluorobenzaldehyde

Product 1

HCID 871189052,3,4'-Trifluorobiphenyl-4-carbaldehydeYield 80.1%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

(4-Fluorophenyl)boronic acid (6.67 g), dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (1.96 g), a 2 M aqueous sodium carbonate solution (47.6 mL), and tris(dibenzylideneacetone)dipalladium(0) (2.04 g) were added at room temperature to a toluene (200 mL) solution of 4-bromo-2,3-difluorobenzaldehyde (7.02 g), and the mixture was stirred at 100° C. for 16 hours in an argon atmosphere. Water was added to the reaction mixture at room temperature, and the mixture was filtered through celite. Then, the filtrate was subjected to extraction with ethyl acetate. The obtained organic layer was 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 passed through a short silica gel column (hexane/ethyl acetate), and the solvent was distilled off under reduced pressure. The obtained residue was crystallized (hexane/ethyl acetate) and further recrystallized (hexane/ethyl acetate) to obtain the title compound (6.01 g).

Workup

  1. filtrationthe mixture was filtered through celite
  2. extractionThen, the filtrate was subjected to extraction with ethyl acetate
  3. washThe obtained organic layer was 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. distillationthe solvent was distilled off under reduced pressure
  7. customThe obtained residue was crystallized (hexane/ethyl acetate)
  8. customfurther recrystallized (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-4c583975318b436cbbdc188b0163c6a1
Source dataset
uspto-grants-2016_05
Patent number
US09353108B2

Reaction notes

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