反应详情

A solution of dibenzyl dicarboxylate (10.1 g, 33.9 mmol) in tetrahydrofuran (50 ml) was added dropwise to a mixture of the 5-hydroxy-4-methyl-1H-indazole (4.17 g, 28.1 mmol) obtained in Example 402, t-butyl 3-hydroxypiperidine-1-carboxylate (5.62 g, 27.9 mmol) and tetrahydrofuran (100 ml) under ice-cooling. After 30 minutes, the mixture thus obtained was warmed up to room temperature and stirred for 16 hours. The reaction mixture was concentrated and then a 1N-aqueous sodium hydroxide solution (250 ml) was added thereto, followed by extraction with chloroform (150 ml) (three times). The organic layer was washed with a saturated aqueous sodium chloride solution and dried over magnesium sulfate. The solvent was distilled off under reduced pressure and the resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate=3/1 to 2/1) to obtain a crude product t-butyl 3-[(4-methyl-1H-indazol-5-yl)oxy]piperidine-1-carboxylate (a mixture with t-butyl 3-hydroxypiperidine-1-carboxylate, 3.46 g).

1. temperaturecooling
2. customthe mixture thus obtained
3. concentrationThe reaction mixture was concentrated
4. additiona 1N-aqueous sodium hydroxide solution (250 ml) was added
5. extractionfollowed by extraction with chloroform (150 ml) (three times)
6. washThe organic layer was washed with a saturated aqueous sodium chloride solution
7. dry with materialdried over magnesium sulfate
8. distillationThe solvent was distilled off under reduced pressure
9. customthe resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate=3/1 to 2/1)