反应详情

温度

0 °C

tert-Butyl 6-bromoindazole-3-carboxylate was prepared from the acid by reaction with a 2-fold excess of di-tert-butyldicarbonate followed by treatment with sodium hydroxide. To a suspension of sodium hydride (60% mineral oil dispersion) (4.8 mmol) in tetrahydrofuran (40 mL) at 0° C. was slowly added a solution of tert-butyl 6-bromoindazole-3-carboxylate (4.0 mmol) in tetrahydrofuran (4 mL). After stirring for 0.5 h at 0° C., the mixture was cooled to −78° C. and a 1.7 M solution of tert-butyllithium in pentane (5.1 mmol) was added. After 0.5 h at −78° C., a solution of tetrahydropyran-4-one (5 mmol) in tetrahydrofuran (1 mL) was added dropwise. The mixture was stirred at −78° C. for 1 h and warmed to 0° C. The reaction mixture was quenched with saturated aqueous ammonium chloride and the mixture was partitioned between ethyl acetate (100 mL) and water (100 mL). The organic layer was separated, washed with brine (50 mL), dried (magnesium sulfate), and concentrated. The residue was purified by chromatography (70/30 ethyl acetate/hexanes) to yield 6-(4-hydroxytetrahydropyran-4-yl)-1H-indazole-3-carboxylic acid tert-butyl ester (68%) as a colorless solid.

1. temperaturethe mixture was cooled to −78° C.
2. waitAfter 0.5 h at −78° C.
3. stirringThe mixture was stirred at −78° C. for 1 h
4. temperaturewarmed to 0° C
5. customThe reaction mixture was quenched with saturated aqueous ammonium chloride
6. customthe mixture was partitioned between ethyl acetate (100 mL) and water (100 mL)
7. customThe organic layer was separated
8. washwashed with brine (50 mL)
9. dry with materialdried (magnesium sulfate)
10. concentrationconcentrated
11. customThe residue was purified by chromatography (70/30 ethyl acetate/hexanes)