反应详情

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.

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