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

HRID 70629

Reaktionsgleichung

Reaktionsgleichung von HRID 70629
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:27]=[CH:26][C:25](B(O)O)=[CH:24][CH:23]=1.O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(OCC)(=O)C.O.O1CCOCC1>[Cl:21][C:22]1[CH:27]=[CH:26][C:25](/[C:2](/[C:10]2[CH:15]=[CH:14][C:13]([CH:16]3[CH2:18][CH2:17]3)=[C:12]([O:19][CH3:20])[N:11]=2)=[CH:3]\[C@@H:4]2[NH:8][C:7](=[O:9])[CH2:6][CH2:5]2)=[CH:24][CH:23]=1

Komponenten

9

Edukt 4

HCID 10796Cesium carbonateHCID 742994-Chlorophenylboronic acidHCID 521585Tris(furan-2-yl)phosphaneHCID 58452792(5R)-5-[(Z)-2-bromo-2-(5-cyclopropyl-6-methoxypyridin-2-yl)ethenyl]pyrrolidin-2-one

Produkt 1

HCID 67399304(5R)-5-[(E)-2-(4-chlorophenyl)-2-(5-cyclopropyl-6-methoxypyridin-2-yl)ethenyl]pyrrolidin-2-one

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 9832798Tris(dibenzylideneacetone) dipalladiumKatalysatorHCID 962WaterLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

1,4-Dioxane (4 mL) and water (0.4 mL) were added to a mixture of (5R)-5-[(Z)-2-bromo-2-(5-cyclopropyl-6-methoxypyridin-2-yl)ethenyl]pyrrolidin-2-one obtained in Reference Example 4-24 (170 mg), 4-chlorophenylboronic acid (160 mg), tris(dibenzylideneacetone) dipalladium (45 mg), tri(2-furyl)phosphine (69 mg) and cesium carbonate (492 mg), and the mixture was stirred at 90° C. for 2.5 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-(4-chlorophenyl)-2-(5-cyclopropyl-6-methoxypyridin-2-yl)ethenyl]pyrrolidin-2-one as a crude product (250 mg).

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-1ddef37346744936946e7026649bb908
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08822503B2

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