反应详情

Under a nitrogen atmosphere, triphenylphosphine (280 mg, 1.07 mmol), tert-butyl 4-hydroxypiperidine-1-carboxylate (179 mg, 0.890 mmol) and diisopropyl azodicarboxylate (193 μl, 0.979 mmol) were added at 0° C. to a solution of the 4-chloro-1H-indazol-5-ol (150 mg, 0.890 mmol) obtained in Example 468 in tetrahydrofuran (6 ml). After 30 minutes, the mixture thus obtained was heated to room temperature and stirred overnight. The reaction solution was concentrated under reduced pressure, and the resulting residue was diluted with chloroform and then washed with a 1M-aqueous sodium hydroxide solution. After the aqueous layer was re-extracted with chloroform, 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 oil thus obtained was dissolved in methanol (3 ml) at room temperature and 4N-hydrochloric acid-dioxane (3 ml) was added thereto. After 1 hour, the mixture thus obtained was concentrated under reduced pressure and the resulting residue was washed with ethyl acetate by repulping to obtain 5-(piperidin-4-yloxy)-4-chloro-1H-indazole hydrochloride (219.7 mg, 86%).

1. customthe mixture thus obtained
2. concentrationThe reaction solution was concentrated under reduced pressure
3. additionthe resulting residue was diluted with chloroform
4. washwashed with a 1M-aqueous sodium hydroxide solution
5. extractionAfter the aqueous layer was re-extracted with chloroform
6. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
7. customThe organic layer dried
8. concentrationwas concentrated under reduced pressure
9. customthe resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate)
10. customThe oil thus obtained
11. waitAfter 1 hour
12. customthe mixture thus obtained
13. concentrationwas concentrated under reduced pressure
14. washthe resulting residue was washed with ethyl acetate