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 the crystal (21.8 g) was filtered (the crystal is the crystal mentioned in Example 23). The resultant crystal was dissolved by heating at 60° C. in a mixed solution of methyl-tert-butyl ether (833 mL) and acetonitrile (167 mL). The solution was recrystallized by being left to stand at room temperature, and the crystal (7.39 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 having the following physical properties (4.11 g, 88% ee). 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. filtrationthe crystal (21.8 g) was filtered (the crystal
7. dissolutionThe resultant crystal was dissolved
8. customThe solution was recrystallized
9. waitby being left
10. customto stand at room temperature
11. filtrationthe crystal (7.39 g) was filtered
12. additionThe resultant crystal was diluted with a mixed solution of an aqueous saturated sodium hydrogen carbonate solution and saturated brine
13. extractionextracted five times with ethyl acetate
14. washThe organic layer was washed with a mixed solution of an aqueous saturated sodium hydrogen carbonate solution and saturated brine
15. dry with materialThe organic layer was dried over anhydrous sodium sulfate
16. concentrationconcentrated under reduced pressure