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

HRID 131048

Reaktionsgleichung

Reaktionsgleichung von HRID 131048
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

Komponenten

4

Edukt 2

HCID 597300371-(4-Methoxy-benzyl)-piperidine-3-carboxylic acid methoxy-methyl-amideHCID 178455855HCID 178455855, Verbindung

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-8f9c19ff6a8544af9021320c748be8be
Quelldatensatz
uspto-grants-2008_06
Patentnummer
US07381719B2

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