Dimethylformamide → 3′,4-Difluoro[1,1′-biphenyl]-3-carboxaldehyde

HRID 1771806Notes

Reaction equation

HRID 1771806 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([F:10])=[C:6]([CH:9]=1)[CH:7]=[O:8].[F:11][C:12]1[CH:13]=[C:14](B(O)O)[CH:15]=[CH:16][CH:17]=1.C([O-])([O-])=O.[K+].[K+].CN(C=O)C>CCO.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[F:10][C:5]1[CH:4]=[CH:3][C:2]([C:16]2[CH:15]=[CH:14][CH:13]=[C:12]([F:11])[CH:17]=2)=[CH:9][C:6]=1[CH:7]=[O:8]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 7363275-Bromo-2-fluorobenzaldehydeHCID 27339863-Fluorophenylboronic acid

Product 1

HCID 463122473′,4-Difluoro[1,1′-biphenyl]-3-carboxaldehydeYield 34.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred mixture of 5-bromo-2-fluoro-benzaldehyde (3.0 g, 14.8 mmol, 1 eq), (3-fluorophenyl)boronic acid (2.48 g, 17.7 mmol, 1.2 eq) and K2CO3 (4.13 g, 44.4 mmol, 3 eq) in a mixture of EtOH (30 mL), DMF (30 mL) and water (10 mL) under N2 was added Pd(PPh3)4 (1.71 g, 1.48 mmol, 0.1 eq). The reaction was heated at 100° C. for 3 h, then filtered through Celite. The filtrate was diluted with water and extracted with EtOAc. The combined organic extracts were washed with water and brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue obtained was purified by column chromatography (petroleum ether:EtOAc, 300:1) to give the title compound as a yellow oil (1.1 g, 34%).

Workup

  1. filtrationfiltered through Celite
  2. additionThe filtrate was diluted with water
  3. extractionextracted with EtOAc
  4. washThe combined organic extracts were washed with water and brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customThe residue obtained
  9. customwas purified by column chromatography (petroleum ether:EtOAc, 300:1)

Sources & evidence

ORD record
ord-06d61654a77e481a98f85b91852f8995
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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