Chloride → 1-[1-(4-Methoxy-benzyl)-piperidin-3-yl]-butan-1-one

HRID 492652

Reaction equation

HRID 492652 reaction equation
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].[Cl-].[CH2:23]1[CH2:27]OC[CH2:24]1>>[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])[CH2:24][CH2:23][CH3:27])[CH2:7]2)=[CH:18][CH:17]=1

Participants

4

Reactant 3

HCID 312ChlorideHCID 8028TetrahydrofuranHCID 597300371-(4-Methoxy-benzyl)-piperidine-3-carboxylic acid methoxy-methyl-amide

Product 1

HCID 597301981-[1-(4-Methoxy-benzyl)-piperidin-3-yl]-butan-1-oneYield 94%

Procedure

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 Propylmagesium 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, n), 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.

Workup

  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

Sources & evidence

ORD record
ord-f8d1885499ac400ab2c2ca5df94498c1
Source dataset
uspto-grants-2009_05
Patent number
US07531557B2

Linked notes

Loading…