反应详情

温度

-78 °C

To a diethyl ether (100 mL) solution of 5-bromo-2-(3-fluoro-phenoxy)-pyridine (5.81 g, 21.7 mmol) described in Manufacturing Example 71-1-1 was added n-butyl lithium (13.8 mL, 1.57 M n-hexane solution, 21.7 mmol) under nitrogen atmosphere at −78° C., which was stirred for 40 minutes at −78° C. N,N-Dimethylformamide (2.02 mL, 26.0 mmol) was then added to the mixture at −78° C., and stirred for 25 minutes as the temperature was gradually raised to 0° C. Water was added to the reaction solution at 0° C., which was then extracted with ethyl acetate. The organic layer was separated, washed with 1 N aqueous sodium hydroxide solution and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by silica gel column chromatography (heptane:ethyl acetate=5:1) to obtain the title compound (2.47 g, 52%).

1. stirringstirred for 25 minutes as the temperature
2. temperaturewas gradually raised to 0° C
3. extractionwhich was then extracted with ethyl acetate
4. customThe organic layer was separated
5. washwashed with 1 N aqueous sodium hydroxide solution and saturated aqueous sodium chloride
6. dry with materialdried over anhydrous magnesium sulfate
7. filtrationfiltered
8. concentrationThe filtrate was concentrated under a reduced pressure
9. customthe residue was purified by silica gel column chromatography (heptane:ethyl acetate=5:1)