Cesium carbonate → (S)-2-(1-((5H-chromeno[3,4-c]pyridin-8-yl)oxy)-4-methylpentan-2-yl)isoindoline-1,3-dione

HRID 2369489Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2369489
Cl[C:2]1[CH:3]=[CH:4][C:5]2[C:15]3[C:10](=[CH:11][N:12]=[CH:13][CH:14]=3)[CH2:9][O:8][C:6]=2[CH:7]=1.[OH:16][CH2:17][C@@H:18]([N:23]1[C:31](=[O:32])[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:24]1=[O:33])[CH2:19][CH:20]([CH3:22])[CH3:21].C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:14]1[CH:13]=[N:12][CH:11]=[C:10]2[CH2:9][O:8][C:6]3[CH:7]=[C:2]([O:16][CH2:17][C@@H:18]([N:23]4[C:24](=[O:33])[C:25]5[C:30](=[CH:29][CH:28]=[CH:27][CH:26]=5)[C:31]4=[O:32])[CH2:19][CH:20]([CH3:22])[CH3:21])[CH:3]=[CH:4][C:5]=3[C:15]=12

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneHCID 713789222-[(2S)-1-Hydroxy-4-methylpentan-2-yl]-1H-isoindole-1,3(2H)-dioneHCID 866958928-chloro-5H-chromeno[3,4-c]pyridine

Produkt 1

HCID 86695893(S)-2-(1-((5H-chromeno[3,4-c]pyridin-8-yl)oxy)-4-methylpentan-2-yl)isoindoline-1,3-dioneAusbeute 101,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 167845palladium(II) acetateKatalysatorHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a stirred suspension of 8-chloro-5H-chromeno[3,4-c]pyridine (1 g, 4.59 mmol), (S)-2-(1-hydroxy-4-methylpentan-2-yl)isoindoline-1,3-dione (3.43 g, 13.88 mmol), di-tert-butyl(2′,4′,6′-triisopropyl-[1,1′-biphenyl]-2-yl)phosphine (1.17 g, 2.76 mmol) and cesium carbonate (2.245 g, 6.89 mmol) in toluene (4 mL) was added palladium (II) acetate (0.309 g, 1.38 mmol). Nitrogen gas was bubbled through the mixture for 5 min, and then the mixture was heated at 80° C. for 14 h. The reaction was diluted with ethyl acetate (25 mL) and filtered through celite. The filtrate was washed with water (1×20 mL) and brine (1×20 mL), dried over sodium sulfate and concentrated under reduced pressure. The residue was purified via silica gel column chromatography (60% ethyl acetate in hexanes) to afford (S)-2-(1-((5H-chromeno[3,4-c]pyridin-8-yl)oxy)-4-methylpentan-2-yl)isoindoline-1,3-dione (2 g, 4.67 mmol, quantitative yield) as a semi solid. LCMS (ESI) m/e 429 [(M+H)+, calcd for C26H25N2O4 429.2].

Aufarbeitung

  1. customNitrogen gas was bubbled through the mixture for 5 min
  2. additionThe reaction was diluted with ethyl acetate (25 mL)
  3. filtrationfiltered through celite
  4. washThe filtrate was washed with water (1×20 mL) and brine (1×20 mL)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified via silica gel column chromatography (60% ethyl acetate in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-d0a30e31080c4cb0aee1acd09b97d3b0
Quelldatensatz
uspto-grants-2014_04
Patentnummer
US08703953B2

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