Potassium Carbonate → 5-Fluoro-3-[4-(6-fluoro-pyridin-3-yl)-5,5-dimethyl-5h-furan-(2e)-ylidene]-1,3-dihydro-indol-2-one

HRID 333391Notes

Reaction equation

HRID 333391 reaction equation
Br[C:2]1[C:6]([CH3:8])([CH3:7])[O:5]/[C:4](=[C:9]2/[C:10](=[O:19])[NH:11][C:12]3[C:17]/2=[CH:16][C:15]([F:18])=[CH:14][CH:13]=3)/[CH:3]=1.[F:20][C:21]1[N:26]=[CH:25][C:24](B(O)O)=[CH:23][CH:22]=1.C(=O)([O-])[O-].[K+].[K+]>C1COCC1.O>[F:18][C:15]1[CH:16]=[C:17]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10](=[O:19])/[C:9]/2=[C:4]1/[O:5][C:6]([CH3:8])([CH3:7])[C:2]([C:24]2[CH:25]=[N:26][C:21]([F:20])=[CH:22][CH:23]=2)=[CH:3]/1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 2783397(6-Fluoropyridin-3-yl)boronic acidHCID 589263273-[4-Bromo-5,5-dimethyl-5h-furan-(2e)-ylidene]-5-fluoro-1,3-dihydro-indol-2-one

Product 1

HCID 589261685-Fluoro-3-[4-(6-fluoro-pyridin-3-yl)-5,5-dimethyl-5h-furan-(2e)-ylidene]-1,3-dihydro-indol-2-oneYield 48%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

To a mixture or 3-[4-bromo-5,5-dimethyl-5H-furan-(2E)-ylidene]-5-fluoro-1,3-dihydro-indol-2-one (3.24 g, 10.0 mmol), 6-fluoropyridin-3-ylboronic acid (1.8 g, 12 mmol) in THF (150 mL), was added a solution of potassium carbonate (13.8 g, 100 mmol) in water (20 mL). The resulting mixture was deoxygenated by bubbling nitrogen through the reaction mixture for 3 minutes and palladium(0)tetrakis(triphenylphosphine) (578 mg, 5 mol %) was then added. The reaction mixture was heated at 65° C. for 18 hours. The reaction was cooled to room temperature and ethyl acetate (500 mL) added. The organic phase was washed with water (100 mL×2), dried over sodium sulfate, and evaporated to give the crude product, which was purified first by silica gel column chromatography (5% CH3OH/CH2Cl2 elution) and then by titration with ethyl acetate. The resulting product was isolated by filtration and dried under vacuum to provide 5-fluoro-3-[4-(6-fluoro-pyridin-3-yl)-5,5-dimethyl-5H-furan-(2E)-ylidene]-1,3-dihydro-indol-2-one as a yellow solid (1.6 g, yield 48%).

Workup

  1. customThe resulting mixture was deoxygenated
  2. customby bubbling nitrogen through the reaction mixture for 3 minutes
  3. additionpalladium(0)tetrakis(triphenylphosphine) (578 mg, 5 mol %) was then added
  4. temperatureThe reaction was cooled to room temperature
  5. additionethyl acetate (500 mL) added
  6. washThe organic phase was washed with water (100 mL×2)
  7. dry with materialdried over sodium sulfate
  8. customevaporated
  9. customto give the crude product, which
  10. customwas purified first by silica gel column chromatography (5% CH3OH/CH2Cl2 elution)
  11. customThe resulting product was isolated by filtration
  12. customdried under vacuum

Sources & evidence

ORD record
ord-7cd83b4d3ccc4fefb803a8093b667ee0
Source dataset
uspto-grants-2014_11
Patent number
US08877923B2

Reaction notes

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