反应详情

To a solution of 1H-indazol-4-ol (200 mg, 1.49 mmol) in tetrahydrofuran (10 ml) were added tert-butyl 4-hydroxypiperidine-1-carboxylate (300 mg, 1.49 mmol), triphenylphosphine (430 mg, 1.64 mmol) and a 40%-dibenzyl azodicarboxylate-dichloromethane solution (0.855 ml, 1.79 mmol) at 0° C. After 1 hour, the mixture thus obtained was warmed up to room temperature. After stirring overnight, the reaction solution was concentrated under reduced pressure, and the resulting residue was dissolved in chloroform (30 ml) and washed with a 1M-aqueous sodium hydroxide solution (20 ml). Extraction with chloroform (30 ml) was carried out again and the organic layer was dried over anhydrous magnesium sulfate. The organic layer dried was concentrated under reduced pressure and the resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate). The mixture thus obtained was dissolved in methanol (2 ml) and 4N-hydrochloric acid-dioxane (2 ml) was added thereto at room temperature. After 2 hours, the reaction solution was concentrated under reduced pressure, and the resulting residue was dissolved in methanol (5 ml) and the pH was adjusted to 10 by dropwise addition of a 2M aqueous sodium hydroxide solution. The resulting mixed solution was concentrated under reduced pressure, dried and then purified by a silica gel column chromatography (eluent: chloroform/methanol=10/1→chloroform/methanol/(1%-NH3 aq)=10/1) to obtain 4-(piperidin-4-yloxy)-1H-indazole (103 mg, 32%).

1. customat 0° C
2. customthe mixture thus obtained
3. concentrationthe reaction solution was concentrated under reduced pressure
4. dissolutionthe resulting residue was dissolved in chloroform (30 ml)
5. washwashed with a 1M-aqueous sodium hydroxide solution (20 ml)
6. extractionExtraction with chloroform (30 ml)
7. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
8. customThe organic layer dried
9. concentrationwas concentrated under reduced pressure
10. customthe resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate)
11. customThe mixture thus obtained
12. customat room temperature
13. waitAfter 2 hours
14. concentrationthe reaction solution was concentrated under reduced pressure
15. dissolutionthe resulting residue was dissolved in methanol (5 ml)
16. additionthe pH was adjusted to 10 by dropwise addition of a 2M aqueous sodium hydroxide solution
17. additionThe resulting mixed solution
18. concentrationwas concentrated under reduced pressure
19. customdried
20. custompurified by a silica gel column chromatography (eluent: chloroform/methanol=10/1→chloroform/methanol/(1%-NH3 aq)=10/1)