Cesium carbonate → 5-Morpholin-4-yl-1-[4-(2-oxopiperidin-1-yl)phenyl]-2,3-dihydropyridin-6-one

HRID 860837Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 860837
I[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][CH:11]=[C:10]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[C:9]2=[O:20])=[CH:4][CH:3]=1.[NH:21]1[CH2:26][CH2:25][CH2:24][CH2:23][C:22]1=[O:27].C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.[Cu+]>[N:14]1([C:10]2[C:9](=[O:20])[N:8]([C:5]3[CH:6]=[CH:7][C:2]([N:21]4[CH2:26][CH2:25][CH2:24][CH2:23][C:22]4=[O:27])=[CH:3][CH:4]=3)[CH2:13][CH2:12][CH:11]=2)[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1

Komponenten

6

Edukt 3

HCID 10796Cesium carbonateHCID 126652-PiperidoneHCID 222404531-(4-Iodophenyl)-3-morpholino-5,6-dihydropyridin-2(1H)-one

Produkt 1

HCID 223522265-Morpholin-4-yl-1-[4-(2-oxopiperidin-1-yl)phenyl]-2,3-dihydropyridin-6-oneAusbeute 77 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 104815Copper(1+)KatalysatorHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

Part B. Soluble copper(I)-catalyzed Ullmann coupling reaction. A suspension of 1-(4-iodo-phenyl)-3-morpholin-4-yl-5,6-dihydro-1H-pyridin-2-one (10, 2.2 g, 5.73 mmol), piperidin-2-one (42, 851 mg, 8.59 mmol, 1.5 equiv), and Cs2CO3 (3.73 g, 11.46 mmol, 2.0 equiv) in toluene (15 mL) was treated with Cu(PPh3)3Br (1.065 g, 1.146 mmol, 20% equiv) at room temperature under N2, and the resulting reaction mixture was degassed three times under a steady stream of nitrogen. The reaction mixture was warmed up to reflux for 6 h. When HPLC showed the Ullmann coupling reaction was complete, the reaction mixture was cooled down to 5–10° C. before being quenched with 14% of ammonium hydroxide aqueous solution (20 mL) and EtOAc (30 mL) at 5–10° C. The mixture was stirred for an additional 4 h at 25° C. The two layers were then separated, and the aqueous layer was extracted with EtOAc (3×20 mL). The combined organic extracts were washed with saturated NaCl aqueous solution (10 mL), dried over MgSO4, and concentrated in vacuo. The residue was directly purified by flash column chromatography (SiO2, 15–40% EtOAc/hexane gradient elution) to afford the desired 3-morpholin-4-yl-1-[4-(2-oxo-piperidin-1-yl)-phenyl]-5,6-dihydro-1H-pyridin-2-one (63, 1.568 g, 2.036 g theoretical, 77%) as a pale-yellow oil, which solidified upon standing at room temperature in vacuo. For 63, CIMS m/z 356 (M++H, C20H25N3O3).

Aufarbeitung

  1. customreaction
  2. customthe resulting reaction mixture
  3. customwas degassed three times under a steady stream of nitrogen
  4. temperatureThe reaction mixture was warmed up
  5. temperatureto reflux for 6 h
  6. customthe Ullmann coupling reaction
  7. temperaturethe reaction mixture was cooled down to 5–10° C.
  8. custombefore being quenched with 14% of ammonium hydroxide aqueous solution (20 mL) and EtOAc (30 mL) at 5–10° C
  9. customThe two layers were then separated
  10. extractionthe aqueous layer was extracted with EtOAc (3×20 mL)
  11. washThe combined organic extracts were washed with saturated NaCl aqueous solution (10 mL)
  12. dry with materialdried over MgSO4
  13. concentrationconcentrated in vacuo
  14. customThe residue was directly purified by flash column chromatography (SiO2, 15–40% EtOAc/hexane gradient elution)

Quellen und Nachweise

ORD-Eintrag
ord-19f8bd88c9e8479da76c854c2564612b
Quelldatensatz
uspto-grants-2006_12
Patentnummer
US07153960B2

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