Ethyl Acetate → (3E)-6-fluoro-3-[4-(2-fluoropyridin-4-yl)-5,5-dimethylfuran-2(5H)-ylidene]-1,3-dihydro-2H-indol-2-one

HRID 333394

Reaktionsgleichung

Reaktionsgleichung von HRID 333394
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][CH:15]=[C:14]([F:18])[CH:13]=3)/[CH:3]=1.[F:20][C:21]1[CH:26]=[C:25](B(O)O)[CH:24]=[CH:23][N:22]=1.[F-].[K+].C(OCC)(=O)C>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:18][C:14]1[CH:13]=[C:12]2[C:17](/[C:9](=[C:4]3\[O:5][C:6]([CH3:8])([CH3:7])[C:2]([C:25]4[CH:24]=[CH:23][N:22]=[C:21]([F:20])[CH:26]=4)=[CH:3]\3)/[C:10](=[O:19])[NH:11]2)=[CH:16][CH:15]=1

Komponenten

8

Edukt 4

HCID 8857Ethyl AcetateHCID 522689Potassium FluorideHCID 27833962-Fluoropyridine-4-boronic acidHCID 58926029(3E)-3-(4-bromo-5,5-dimethylfuran-2(5H)-ylidene)-6-fluoro-1,3-dihydro-2H-indol-2-one

Produkt 1

HCID 58926164(3E)-6-fluoro-3-[4-(2-fluoropyridin-4-yl)-5,5-dimethylfuran-2(5H)-ylidene]-1,3-dihydro-2H-indol-2-oneAusbeute 57,8 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a mixture of (3E)-3-(4-bromo-5,5-dimethylfuran-2(5H)-ylidene)-6-fluoro-1,3-dihydro-2H-indol-2-one (2.0 g, 6.1 mmol), 2-fluoropyridine-4-boronic acid (1.1 g, 8.0 mmol), potassium fluoride (1.8 g, 5 eq.) in dioxane (50 mL) and water (5 mL) under a nitrogen atmosphere, was added [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (250 mg, 5%). The mixture was heated at 80° C. for 20 hour. The reaction was allowed to cool to room temperature and ethyl acetate (350 mL) was added. The organic phase was washed with water (100 mL×2) and evaporated to provide the crude product. The crude product was purified by column chromatography (silica gel, 5% CH3OH/CH2Cl2 elution) and then recrystallized from ethyl acetate/hexanes (80/20) to provide (3E)-6-fluoro-3-[4-(2-fluoropyridin-4-yl)-5,5-dimethylfuran-2(5H)-ylidene]-1,3-dihydro-2H-indol-2-one as a yellow-orange solid (1.2 g, yield 57%).

Aufarbeitung

  1. temperatureto cool to room temperature
  2. washThe organic phase was washed with water (100 mL×2)
  3. customevaporated
  4. customto provide the crude product
  5. customThe crude product was purified by column chromatography (silica gel, 5% CH3OH/CH2Cl2 elution)
  6. customrecrystallized from ethyl acetate/hexanes (80/20)

Quellen und Nachweise

ORD-Eintrag
ord-7dd9b836973644f09d9e97b5b81d607d
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08877923B2

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