反应详情

温度

5 °C

A solution of 4-amino-1-benzylpiperidine (45.8 g, 0.24 mol) and acetone (531 mL) was stirred at room temperature for 12 hours. The reaction mixture was then reduced to ca. 150 mL in vacuo. To this mixture was added methanol (100 mL) and the resulting mixture was cooled to 5° C. in an ice/water bath. Sodium triacetoxyborohydride (61.2 g, 0.29 mol) in methanol (350 mL), previously cooled to 5° C. in an ice/water bath, was added and this reaction mixture was stirred at 5° C. for 0.5 hours. The ice/water bath was removed and the reaction mixture was stirred for 2 hours at room temperature and then re-cooled to 5° C. in ice/water bath. To this mixture was added concentrated hydrochloric acid (75 mL) until the pH of the reaction mixture was about 3. This mixture was stirred for 1 hour and then concentrated in vacuo to about 600 mL and 1 N aqueous hydrochloric acid (200 mL) was added to dissolve the solids. The aqueous layer was washed with isopropyl acetate (400 mL) and the layers were separated. The aqueous layer was adjusted to pH 12 with 10 N aqueous sodium hydroxide (200 mL) and isopropylacetate (600 mL) was added. This mixture was stirred for 1 hour at room temperature and then the layers were separated and the organic layer washed with saturated aqueous sodium chloride solution (600 mL) and dried over sodium sulfate (80 g). The sodium sulfate was filtered off and washed with ethyl acetate (20 mL). The solvent was removed in vacuo to give 52.0 g of the title intermediate as a yellow oil (95% yield).

1. additionwas added
2. customThe ice/water bath was removed
3. stirringthe reaction mixture was stirred for 2 hours at room temperature
4. temperaturere-cooled to 5° C. in ice/water bath
5. additionTo this mixture was added concentrated hydrochloric acid (75 mL) until the pH of the reaction mixture
6. stirringThis mixture was stirred for 1 hour
7. concentrationconcentrated in vacuo to about 600 mL and 1 N aqueous hydrochloric acid (200 mL)
8. additionwas added
9. dissolutionto dissolve the solids
10. washThe aqueous layer was washed with isopropyl acetate (400 mL)
11. customthe layers were separated
12. additionwas added
13. stirringThis mixture was stirred for 1 hour at room temperature
14. customthe layers were separated
15. washthe organic layer washed with saturated aqueous sodium chloride solution (600 mL)
16. dry with materialdried over sodium sulfate (80 g)
17. filtrationThe sodium sulfate was filtered off
18. washwashed with ethyl acetate (20 mL)
19. customThe solvent was removed in vacuo