反应详情

温度

20 °C

6.85 kg (38.9 mol) 1-benzyl-piperazine (N) were metered into a mixture of 10.00 kg (54.0 mol) ethyl (4-oxo-piperidin-1-yl)-acetate (K), 42 L 2-methyltetrahydrofuran and 11.81 kg (196.7 mol) acetic acid at 20° C. and rinsed with 10.6 L of 2-methyltetrahydrofuran, before the reaction mixture was stirred for one to two hours at 20° C. Then the mixture was metered into the mixture of 12.39 kg (58.5 mol) sodium-triacetoxyborohydride and 36.8 L 2-methyltetrahydrofuran at 20° C., during which time the temperature was allowed to rise to 40° C. After the addition had ended the mixture was rinsed with 15.8 L of 2-methyltetrahydrofuran and the reaction mixture was stirred for at least 1 hour at 40° C. If necessary, further sodium triacetoxyborohydride was added before stirring was continued overnight at 25° C. Once the reaction of the 1-benzylpiperazine was complete the mixture was cooled to 20° C., 52.6 L of water were metered in and the pH was adjusted to 9.0 with 27.3 kg sodium hydroxide solution (50%). After phase separation the organic phase was washed with 26.3 L water and evaporated down completely in vacuo. The residue was taken up in 134 L ethanol and combined with 15.6 kg of 10 molar ethanolic hydrochloric acid (159.4 mol, at least 37.2 wt.-%) at boiling temperature, before the mixture was refluxed for a further 1 hour, with stirring. After cooling to 2° C. and stirring for 1 hour the product was separated off, washed with 31.6 L cold ethanol and dried.

1. washrinsed with 10.6 L of 2-methyltetrahydrofuran, before the reaction mixture
2. customto rise to 40° C
3. additionAfter the addition
4. washwas rinsed with 15.8 L of 2-methyltetrahydrofuran
5. stirringthe reaction mixture was stirred for at least 1 hour at 40° C
6. additionIf necessary, further sodium triacetoxyborohydride was added
7. stirringbefore stirring
8. customOnce the reaction of the 1-benzylpiperazine
9. temperaturewas cooled to 20° C.
10. customAfter phase separation the organic phase
11. washwas washed with 26.3 L water
12. customevaporated down completely in vacuo
13. temperaturebefore the mixture was refluxed for a further 1 hour
14. stirringwith stirring
15. temperatureAfter cooling to 2° C.
16. stirringstirring for 1 hour the product
17. customwas separated off
18. washwashed with 31.6 L cold ethanol
19. customdried