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

HRID 2186134ノート

反応式

HRID 2186134 の反応式
[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

参加物

8

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 679Dimethyl Sulfoxide溶媒2 回HCID 6386tert-Butanol溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-5e8ea939ba704d06b834ec60bddba3ee
出典データセット
uspto-grants-2002_06
特許番号
US06403595B1

反応ノート

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