Ethyl Acetate → 4-{5-[5-fluoro-2-oxo-1,2-dihydro-indol-(3E)-ylidene]-2,2-dimethyl-2,5-dihydro-furan-3-yl}-benzaldehyde

HRID 333384Notes

Reaction equation

HRID 333384 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.[CH:20]([C:22]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][CH:23]=1)=[O:21].C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>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\[CH:3]=[C:2]([C:25]2[CH:26]=[CH:27][C:22]([CH:20]=[O:21])=[CH:23][CH:24]=2)[C:6]([CH3:8])([CH3:7])[O:5]\1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 5910734-Formylphenylboronic AcidHCID 589263273-[4-Bromo-5,5-dimethyl-5h-furan-(2e)-ylidene]-5-fluoro-1,3-dihydro-indol-2-one

Product 1

HCID 589264634-{5-[5-fluoro-2-oxo-1,2-dihydro-indol-(3E)-ylidene]-2,2-dimethyl-2,5-dihydro-furan-3-yl}-benzaldehydeYield 51.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

To a mixture of 3-[4-bromo-5,5-dimethyl-5H-furan-(2E)-ylidene]-5-fluoro-1,3-dihydro-indol-2-one (6.5 g, 20 mmol), 4-formyl phenyl boronic acid (3.6 g, 24 mmol) in THF (250 mL), was added a solution of potassium carbonate (27.6 g, 200 mmol) in water (25 mL). The resulting mixture was deoxygenated with nitrogen, and palladium(0)tetrakis(triphenylphosphine) (1.15 g, 1.0 mmol, 5 mol %) then added. The reaction mixture was heated at 65° C. for 20 hours and then it was allowed to cool to room temperature. Ethyl acetate (800 mL) was added. The organic phase was washed with water (200 mL×2), dried over sodium sulfate and evaporated to give crude product. The purification first by column (SiO2) chromatography (5% CH3OH/CH2Cl2) and then by titration with ethyl acetate led to 4-{5-[5-fluoro-2-oxo-1,2-dihydro-indol-(3E)-ylidene]-2,2-dimethyl-2,5-dihydro-furan-3-yl}-benzaldehyde as a deep red solid (3.6 g, yield 51.5%).

Workup

  1. additionthen added
  2. temperatureto cool to room temperature
  3. washThe organic phase was washed with water (200 mL×2)
  4. dry with materialdried over sodium sulfate
  5. customevaporated
  6. customto give crude product
  7. customThe purification first by column (SiO2) chromatography (5% CH3OH/CH2Cl2)

Sources & evidence

ORD record
ord-1b46a3a2b55e4f3d8229b89fe480fd91
Source dataset
uspto-grants-2014_11
Patent number
US08877923B2

Reaction notes

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