反应详情

温度

67.5 °C

Charge in order, 23.7 g of CH3CN, 10 g of tert-butyl 4,9-diazaspiro[5.5]undecane-9-carboxylate, 9.2 g of K2CO3 then 8.4 g of 4-bromobut-1-yne to R1. Heat the mixture to 65-70° C. and stir the mixture at 65-70° C. for 12-18 hours. Concentrate the mixture to a total weight of 30-40 g below 50° C., then add 76 g of MTBE and 50 g of water. Stir the mixture at 20-25° C. for 30 mins then allow to stand to 30 mins Separate the aqueous. Preopare a solution of 1 g of KOH in 49 g of water and add this to the organic layer at 20-25° C. Stir the mixture at 20-25° C. for 30 mins then allow to stand for 20-30 mins at 20-25° C. Separate the aqueous layer out and wash the organics with 50 g of water. Concentrate the organic phase to 40-50 g total weight below 50° C. in R1. Prepare a solution of 7.4 g of oxalic acid dihydrate in 39.5 g of acetone, then add drop wise the oxalic acid/acetone solution into R1 at 20-25° C. Stir the suspension at 20-25° C. for 2-3 hours then filter. Wash the cake with 15.2 g of MTBE. Slurry the cake in 89 g of THF and stir the mixture at 50° C. for 6-8 hours. Cool the mixture to 20-25° C. and filter. Wash the cake with 17.8 g of THF. Again, slurry the cake in 89 g of THF and stir the mixture at 50° C. for 6-8 hours. Cool the mixture to 20-25° C. and filter. Wash the cake with 17.8 g of THF. Dry the cake under vacuum at 50-60° C. for 16-18 hours to provide the title compound, tert-butyl 4-but-3-ynyl-4,9-diazaspiro[5.5]undecane-9-carboxylate; oxalic acid.

1. concentrationConcentrate the mixture to a total weight of 30-40 g below 50° C.
2. additionadd 76 g of MTBE and 50 g of water
3. stirringStir the mixture at 20-25° C. for 30 mins
4. waitto stand to 30 mins
5. customSeparate the aqueous
6. additionPreopare a solution of 1 g of KOH in 49 g of water and add this to the organic layer at 20-25° C
7. stirringStir the mixture at 20-25° C. for 30 mins
8. waitto stand for 20-30 mins at 20-25° C
9. customSeparate the aqueous layer out and
10. washwash the organics with 50 g of water
11. concentrationConcentrate the organic phase to 40-50 g total weight below 50° C. in R1
12. customPrepare a solution of 7.4 g of oxalic acid dihydrate in 39.5 g of acetone
13. stirringStir the suspension at 20-25° C. for 2-3 hours
14. filtrationthen filter
15. washWash the cake with 15.2 g of MTBE
16. stirringstir the mixture at 50° C. for 6-8 hours
17. temperatureCool the mixture to 20-25° C.
18. filtrationfilter
19. washWash the cake with 17.8 g of THF
20. stirringstir the mixture at 50° C. for 6-8 hours
21. temperatureCool the mixture to 20-25° C.
22. filtrationfilter
23. washWash the cake with 17.8 g of THF
24. customDry the cake under vacuum at 50-60° C. for 16-18 hours