反应详情

Under a nitrogen atmosphere, a 1.57M-n-butyllithium/hexane solution (12.00 ml, 0.0189 mol) was added dropwise to a solution of the 4-bromo-1-tetrahydro-2H-pyran-2-yl-5-(tetrahydro-2H-pyran-2-yloxy)-1H-indazole (6.0 g, 0.0157 mol) obtained in Example 607 in tetrahydrofuran (120 ml) at −78° C. over a period of 15 minutes. After 30 minutes, a solution of trimethoxyborane (2.65 ml, 0.0236 mol) in tetrahydrofuran (30 ml) was added dropwise thereto over a period of 5 minutes and the resulting mixture was slowly heated. After 15 hours, acetic acid (1.98 ml, 0.0346 mol) was added thereto. After 15 minutes, a solution of 30%-aqueous hydrogen peroxide solution (4.46 ml, 0.0393 mol) in tetrahydrofuran (20 ml) was added dropwise thereto over a period of 10 minutes, and the resulting mixture was slowly heated to room temperature. After 8.5 hours, a 30%-aqueous hydrogen peroxide solution (4.72 mmol) was further added thereto. After 15 hours, a 10%-aqueous sodium hydrogensulfite solution and a saturated aqueous sodium hydrogencarbonate solution were added thereto, and the resulting mixture was poured into water and extracted with ethyl acetate. The extract solution was concentrated under reduced pressure and the resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate). The residue purified was concentrated under reduced pressure and the resulting residue was washed with hexane by repulping to obtain 1-tetrahydro-2H-pyran-2-yl-5-(tetrahydro-2H-pyran-2-yloxy)-1H-indazol-4-ol (2.9892 g, 42%).

1. waitover a period of 5 minutes
2. temperaturethe resulting mixture was slowly heated
3. waitAfter 15 hours
4. waitAfter 15 minutes
5. waitover a period of 10 minutes
6. waitAfter 8.5 hours
7. waitAfter 15 hours
8. extractionextracted with ethyl acetate
9. concentrationThe extract solution was concentrated under reduced pressure
10. customthe resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate)
11. customThe residue purified
12. concentrationwas concentrated under reduced pressure
13. washthe resulting residue was washed with hexane