Cesium carbonate → (5R)-5-[(E)-2-(5-cyclopropyl-6-methoxypyridin-2-yl)-2-(3,4-dichlorophenyl)ethenyl]pyrrolidin-2-one

HRID 70679Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 70679
Br/[C:2](/[C:10]1[CH:15]=[CH:14][C:13]([CH:16]2[CH2:18][CH2:17]2)=[C:12]([O:19][CH3:20])[N:11]=1)=[CH:3]\[C@@H:4]1[NH:8][C:7](=[O:9])[CH2:6][CH2:5]1.[Cl:21][C:22]1[CH:23]=[C:24](OB(O)O)[CH:25]=[CH:26][C:27]=1[Cl:28].O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>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].C(OCC)(=O)C.O.O1CCOCC1>[CH:16]1([C:13]2[CH:14]=[CH:15][C:10](/[C:2](/[C:25]3[CH:24]=[CH:23][C:22]([Cl:21])=[C:27]([Cl:28])[CH:26]=3)=[CH:3]/[C@@H:4]3[NH:8][C:7](=[O:9])[CH2:6][CH2:5]3)=[N:11][C:12]=2[O:19][CH3:20])[CH2:18][CH2:17]1

Komponenten

9

Edukt 4

HCID 10796Cesium carbonateHCID 521585Tris(furan-2-yl)phosphaneHCID 219399273,4-Dichloro-phenyl-boric acidHCID 58452792(5R)-5-[(Z)-2-bromo-2-(5-cyclopropyl-6-methoxypyridin-2-yl)ethenyl]pyrrolidin-2-one

Produkt 1

HCID 67397284(5R)-5-[(E)-2-(5-cyclopropyl-6-methoxypyridin-2-yl)-2-(3,4-dichlorophenyl)ethenyl]pyrrolidin-2-one

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 962WaterLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

1,4-Dioxane (4 mL) and water (0.5 mL) were added to a mixture of (5R)-5-[(Z)-2-bromo-2-(5-cyclopropyl-6-methoxypyridin-2-yl)ethenyl]pyrrolidin-2-one (300 mg), 3,4-dichlorophenylboric acid (340 mg), tris(dibenzylideneacetone)dipalladium (81 mg), tri(2-furyl) phosphine (124 mg) and cesium carbonate (867 mg), and the mixture was stirred at 90° C. for three hours. Water and ethyl acetate were added to the reaction solution and the insoluble matter was filtered off through celite, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=50:50→0:100) to give (5R)-5-[(E)-2-(5-cyclopropyl-6-methoxypyridin-2-yl)-2-(3,4-dichlorophenyl)ethenyl]pyrrolidin-2-one as a colorless amorphous (250 mg, 69%).

Aufarbeitung

  1. filtrationthe insoluble matter was filtered off through celite
  2. extractionfollowed by extraction with ethyl acetate
  3. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customThe resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=50:50→0:100)

Quellen und Nachweise

ORD-Eintrag
ord-46abfe357f1a462e887b20e9281d55dc
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08822503B2

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