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

HRID 2186134Notes

Reaction equation

HRID 2186134 reaction equation
[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

Participants

8

Reactant 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

Product 1

HCID 234475964-Benzyloxycarbonyl-1-[4-hydroxy-1-(4-pyridyl)piperidin-4-ylmethyl]-2-oxo-1,2,3,4-tetrahydropyrazineYield 108.3%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 6386tert-ButanolSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-5e8ea939ba704d06b834ec60bddba3ee
Source dataset
uspto-grants-2002_06
Patent number
US06403595B1

Reaction notes

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