反应详情

温度

-78 °C

To a solution of tert-butyl 4-(6-{2-[4-(ethoxycarbonyl)-2-fluorophenyl]ethyl}pyridin-3-yl)piperazine-1-carboxylate (1.414 g, 3.091 mmol) in anhydrous tetrahydrofuran (15 ml) was added dropwise at −78° C. 1M diisobutylaluminum hydride tetrahydrofuran solution (12 ml, 12 mmol) over 10 mins. After stirring at −78° C. for 30 mins, the mixture was heated to room temperature and stirred for 1 hr 40 mins. After cooling to −78° C., 1M diisobutylaluminum hydride tetrahydrofuran solution (6 ml, 6 mmol) was added dropwise over 5 mins. The mixture was heated to room temperature and stirred for 40 mins. Saturated aqueous potassium sodium tartrate solution (150 ml) was added and the mixture was stirred and extracted 3 times with ethyl acetate. The combined organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=4:1→ethyl acetate) to give tert-butyl 4-(6-{2-[2-fluoro-4-(hydroxymethyl)phenyl]ethyl}pyridin-3-yl)piperazine-1-carboxylate (1.046 g, yield 81.4%) as a slightly yellow solid.

1. temperaturethe mixture was heated to room temperature
2. stirringstirred for 1 hr 40 mins
3. temperatureAfter cooling to −78° C.
4. temperatureThe mixture was heated to room temperature
5. stirringstirred for 40 mins
6. stirringthe mixture was stirred
7. extractionextracted 3 times with ethyl acetate
8. washThe combined organic layer was washed with saturated brine
9. dry with materialdried over anhydrous magnesium sulfate
10. concentrationconcentrated under reduced pressure
11. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=4:1→ethyl acetate)