反应详情

温度

60 °C

8-tert-butyl 3-ethyl 2,8-diazaspiro[4.5]decane-3,8-dicarboxylate (Japanese Unexamined Patent Publication (Kokai) No. 2004-002470, Example 21f; 25.0 g) and (S)-(+)-camphorsulfonic acid (18.6 g) were dissolved in acetonitrile (100 mL) and concentrated under reduced pressure. To the residue, methyl-tert-butyl ether (250 mL) was added and recrystallization was carried out by being left to stand at room temperature, and then a crystal was filtered (the crystal is used in Example 24). The filtrate was concentrated under reduced pressure and the resultant residue was diluted with a mixed solution of an aqueous saturated sodium hydrogen carbonate solution and saturated brine, and then extracted three times with ethyl acetate. The organic layer was washed with a mixed solution of an aqueous saturated sodium hydrogen carbonate solution and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. To the residue, (R)-(−)-camphorsulfonic acid (8.97 g) was added and the mixture was dissolved in acetonitrile (121 mL) and then concentrated under reduced pressure. To the residue, a mixed solution of acetonitrile (4 mL) and methyl-tert-butyl ether (121 mL) were added and crystallization was carried out by being left to stand at room temperature, and then a crystal (9.98 g) was filtered. The resultant crystal was dissolved by heating at 60° C. in a mixed solution of methyl-tert-butyl ether (425 mL) and acetonitrile (85 mL). The solution was recrystallized by being left to stand at room temperature, and a crystal (6.18 g) was filtered. The resultant crystal was diluted with a mixed solution of an aqueous saturated sodium hydrogen carbonate solution and saturated brine, and then extracted five times with ethyl acetate. The organic layer was washed with a mixed solution of an aqueous saturated sodium hydrogen carbonate solution and saturated brine. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain the title compound (3.63 g, 99% ee) having the following physical properties. Optical purity was confirmed using a high-performance liquid chromatography (HPLC).

1. concentrationconcentrated under reduced pressure
2. additionTo the residue, methyl-tert-butyl ether (250 mL) was added
3. customrecrystallization
4. waitby being left
5. customto stand at room temperature
6. filtrationa crystal was filtered (the crystal
7. concentrationThe filtrate was concentrated under reduced pressure
8. additionthe resultant residue was diluted with a mixed solution of an aqueous saturated sodium hydrogen carbonate solution and saturated brine
9. extractionextracted three times with ethyl acetate
10. washThe organic layer was washed with a mixed solution of an aqueous saturated sodium hydrogen carbonate solution and saturated brine
11. dry with materialdried over anhydrous magnesium sulfate
12. concentrationconcentrated under reduced pressure
13. additionTo the residue, (R)-(−)-camphorsulfonic acid (8.97 g) was added
14. dissolutionthe mixture was dissolved in acetonitrile (121 mL)
15. concentrationconcentrated under reduced pressure
16. additionTo the residue, a mixed solution of acetonitrile (4 mL) and methyl-tert-butyl ether (121 mL) were added
17. customcrystallization
18. waitby being left
19. customto stand at room temperature
20. filtrationa crystal (9.98 g) was filtered
21. dissolutionThe resultant crystal was dissolved
22. customThe solution was recrystallized
23. waitby being left
24. customto stand at room temperature
25. filtrationa crystal (6.18 g) was filtered
26. additionThe resultant crystal was diluted with a mixed solution of an aqueous saturated sodium hydrogen carbonate solution and saturated brine
27. extractionextracted five times with ethyl acetate
28. washThe organic layer was washed with a mixed solution of an aqueous saturated sodium hydrogen carbonate solution and saturated brine
29. dry with materialThe organic layer was dried over anhydrous sodium sulfate
30. concentrationconcentrated under reduced pressure