Cesium carbonate → (5S)-1-(6-chloropyridin-3-yl)-5-(piperidin-1-ylmethyl)pyrrolidin-2-one

HRID 548645ノート

反応式

HRID 548645 の反応式
Br[C:2]1[CH:3]=[CH:4][C:5]([Cl:8])=[N:6][CH:7]=1.[N:9]1([CH2:15][C@H:16]2[NH:20][C:19](=[O:21])[CH2:18][CH2:17]2)[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1>[Cl:8][C:5]1[N:6]=[CH:7][C:2]([N:20]2[C@H:16]([CH2:15][N:9]3[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14]3)[CH2:17][CH2:18][C:19]2=[O:21])=[CH:3][CH:4]=1

参加物

6

反応物 3

HCID 10796Cesium carbonateHCID 27344145-Bromo-2-chloropyridineHCID 57550249(5S)-5-(piperidin-1-ylmethyl)pyrrolidin-2-one

生成物 1

HCID 57550242(5S)-1-(6-chloropyridin-3-yl)-5-(piperidin-1-ylmethyl)pyrrolidin-2-one収率 44%

試薬・触媒・溶媒 2

HCID 9832798Tris(dibenzylideneacetone) dipalladium触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

A suspension of 5-bromo-2-chloropyridine a130 (0.75 g, 3.9 mmol, 1 eq), (5S)-5-(piperidin-1-ylmethyl)pyrrolidin-2-one a15 (0.85 g, 4.67 mmol, 1.2 eq), cesium carbonate (1.78 g, 5.46 mmol, 1.4 eq), Xanphos (0.17 g, 0.29 mmol, 0.075 eq), and tris(dibenzylideneacetone) dipalladium (0) (89 mg, 0.097 mmol, 0.025 eq) in dioxane (25 ml) is stirred under an argon atmosphere in a sealed tube for 12 h at 100° C. The mixture is left to cool to room temperature and filtered through a pad of Celite. The solid is washed with ethyl acetate and the resulting soluble fractions are combined and concentrated to dryness. The residue is taken up in ethyl acetate and washed twice with a saturated aqueous solution of sodium hydrogenocarbonate. The organic phase is then dried over magnesium sulfate and concentrated to afford 1.4 g of crude mixture. Purification by chromatography over silicagel (dichloromethane/methanol/ammonia gradient) affords 0.5 g of (5S)-1-(6-chloropyridin-3-yl)-5-(piperidin-1-ylmethyl)pyrrolidin-2-one a131.

後処理

  1. waitThe mixture is left
  2. temperatureto cool to room temperature
  3. filtrationfiltered through a pad of Celite
  4. washThe solid is washed with ethyl acetate
  5. concentrationconcentrated to dryness
  6. washwashed twice with a saturated aqueous solution of sodium hydrogenocarbonate
  7. dry with materialThe organic phase is then dried over magnesium sulfate
  8. concentrationconcentrated
  9. customto afford 1.4 g of crude mixture
  10. customPurification by chromatography over silicagel (dichloromethane/methanol/ammonia gradient)

出典と根拠

ORDレコード
ord-43988d10efed46759a5952101fb04c40
出典データセット
uspto-grants-2011_05
特許番号
US07943605B2

反応ノート

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