Sodium hydride → 4-Benzyloxycarbonyl-1-[4-hydroxy-1-(4-pyridyl)piperidin-4-ylmethyl]-2-oxo-1,2,3,4-tetrahydropyrazine

HRID 1840546Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1840546
[H-].[Na+].[I-].C[S+](C)(C)=O.[N:9]1[CH:14]=[CH:13][C:12]([N:15]2[CH2:20][CH2:19][C:18](=[O:21])[CH2:17][CH2:16]2)=[CH:11][CH:10]=1.[CH2:22]([O:29][C:30]([N:32]1[CH:37]=[CH:36][NH:35][C:34](=[O:38])[CH2:33]1)=[O:31])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.[CH3:39]C(C)([O-])C.[K+]>CS(C)=O.C(O)(C)(C)C>[CH2:22]([O:29][C:30]([N:32]1[CH:37]=[CH:36][N:35]([CH2:39][C:18]2([OH:21])[CH2:19][CH2:20][N:15]([C:12]3[CH:13]=[CH:14][N:9]=[CH:10][CH:11]=3)[CH2:16][CH2:17]2)[C:34](=[O:38])[CH2:33]1)=[O:31])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Komponenten

8

Edukt 5

HCID 24758Sodium hydrideHCID 74498Sulfoxonium, trimethyl-, iodide (1:1)HCID 113327931-(Pyridin-4-yl)piperidin-4-oneHCID 234473834-Benzyloxycarbonyl-1,2,3,4-tetrahydropyrazin-2-oneHCID 23665647Potassium tert-butoxide

Produkt 1

HCID 234475964-Benzyloxycarbonyl-1-[4-hydroxy-1-(4-pyridyl)piperidin-4-ylmethyl]-2-oxo-1,2,3,4-tetrahydropyrazineAusbeute 108,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 679Dimethyl SulfoxideLösungsmittel2×HCID 6386tert-ButanolLösungsmittel

Versuchsvorschrift

To a suspension of sodium hydride in oil (2.35 g) in dimethylsulfoxide (100 ml) was added portionwise, under ice-cooling, trimethylsulfoxonium iodide (13.5 g), and the mixture was stirred at room temperature for 30 minutes to give a uniform solution. To the reaction solution was added dropwise a solution of 1-(4-pyridyl)-4-piperidinone (9.0 g) in dimethylsulfoxide (20 ml), under ice-cooling, and the mixture was stirred at room temperature for 2 hours. To the reaction solution were added 4-benzyloxycarbonyl-2-oxo-1,2,3,4-tetrahydropyrazine (11.8 g), potassium t-butoxide (1.7 g) and t-butanol (200 ml), and the mixture was stirred at 80° C. for 15 hours. The reaction solution was concentrated, and to the residue was added water. The mixture was extracted with dichloromethane, washed with brine, dried and concentrated, and the resulting residue was purified with silica gel column chromatography (dichloromethane: methanol containing 10% ammonia solution=20:1) to give colorless amorphous of the title compound (6.93 g).

Aufarbeitung

  1. additionwas added portionwise, under ice-
  2. temperaturecooling
  3. customto give a uniform solution
  4. temperatureunder ice-cooling
  5. stirringthe mixture was stirred at 80° C. for 15 hours
  6. concentrationThe reaction solution was concentrated
  7. additionto the residue was added water
  8. extractionThe mixture was extracted with dichloromethane
  9. washwashed with brine
  10. customdried
  11. concentrationconcentrated
  12. customthe resulting residue was purified with silica gel column chromatography (dichloromethane: methanol containing 10% ammonia solution=20:1)

Quellen und Nachweise

ORD-Eintrag
ord-051b08f007bb453e9d810fa52deb9caa
Quelldatensatz
uspto-grants-2004_01
Patentnummer
US06680312B2

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