1-(4-Methoxy-benzyl)-piperidine-3-carboxylic acid methoxy-methyl-amide → 1-[1-(4-Methoxy-benzyl)-piperidin-3-yl]-butan-1-one

HRID 131048

反応式

HRID 131048 の反応式
CON(C)[C:4]([CH:6]1[CH2:11][CH2:10][CH2:9][N:8]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)[CH2:7]1)=[O:5].[CH2:22]([Mg]Cl)[CH2:23][CH3:24]>C1COCC1>[CH3:20][O:19][C:16]1[CH:15]=[CH:14][C:13]([CH2:12][N:8]2[CH2:9][CH2:10][CH2:11][CH:6]([C:4](=[O:5])[CH2:22][CH2:23][CH3:24])[CH2:7]2)=[CH:18][CH:17]=1

参加物

4

反応物 2

HCID 597300371-(4-Methoxy-benzyl)-piperidine-3-carboxylic acid methoxy-methyl-amideHCID 178455855HCID 178455855、化合物

生成物 1

HCID 597301981-[1-(4-Methoxy-benzyl)-piperidin-3-yl]-butan-1-one収率 94.4%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

Combine 1-(4-Methoxy-benzyl)-piperidine-3-carboxylic acid methoxy-methyl-amide (401.0 mg, 1.37 mmol) and THF (10 mL) at 0° C. under a Nitrogen atmosphere. By dropwise addition, add Propylmagnesium chloride (4.0 mL, 8.22 mmol). Reflux the reaction for 5 hours then cool the reaction to room temperature and quench the reaction mixture with sat NH4Cl (aq) and extract product from the water using Ethyl acetate. Wash the organic layer with brine and then dry over Na2SO4. Concentrate under reduced pressure and add to an SCX (5 g) column pre-treated with 5% AcOH/MeOH. Wash with MeOH and elute product using 1N NH3 MeOH to give 356.0 mg (94% yield) of the title compound: 1H NMR (500 MHz, CDCl3); 0.8 (3H, t), 1.3 (1H, qd), 1.4-1.5 (3H, m), 1.6-1.8 (1H, m), 1.9 (1H, dd), 2.0 (1H, td), 2.1 (1H, t), 2.4 (2H, t), 2.5-2.6 (1H, m), 2.7 (1H, d), 2.9 (1H, d), 3.4 (2H, dd), 3.8 (3H, s), 6.8 (2H, d), 7.2 (2H, d); TLC 4% 1N NH3 MeOH:CH2Cl2 Rf=0.42.

後処理

  1. customat 0° C.
  2. additionBy dropwise addition
  3. temperatureReflux
  4. customthe reaction for 5 hours
  5. temperaturethen cool
  6. customthe reaction to room temperature
  7. customquench the reaction mixture with sat NH4Cl (aq)
  8. extractionextract product from the water
  9. washWash the organic layer with brine
  10. dry with materialdry over Na2SO4
  11. concentrationConcentrate under reduced pressure
  12. additionadd to an SCX (5 g) column
  13. additionpre-treated with 5% AcOH/MeOH
  14. washWash with MeOH
  15. washelute product

出典と根拠

ORDレコード
ord-8f9c19ff6a8544af9021320c748be8be
出典データセット
uspto-grants-2008_06
特許番号
US07381719B2

関連ノート

読み込み中…