反应详情

温度

100 °C

To an acetic acid (20 mL) solution of 6-(3-fluoro-phenoxy)-pyridine-3-carbaldehyde (2.47 g, 11.4 mmol) described in Manufacturing Example 71-1-2 was added nitromethane (3.09 mL, 57.0 mmol) and ammonium acetate (1.76 g, 22.8 mmol), which was stirred for 6 hours at 100° C. Water was added to the reaction solution at room temperature, which was then extracted with ethyl acetate. The organic layer was separated, washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure. To a dimethyl sulfoxide (35 mL) and acetic acid (5 mL) solution of the residue was added sodium borohydride (681 mg, 17.1 mmol), which was stirred for 40 minutes at room temperature. Sodium hydrogencarbonate and water were added to the reaction mixture at room temperature while cooling appropriately, which was then extracted with ethyl acetate. The organic layer was separated, washed with 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 NH silica gel column chromatography (heptane:ethyl acetate=2:1) to obtain the title compound (1.96 g, 66%).

1. extractionwhich was then extracted with ethyl acetate
2. customThe organic layer was separated
3. washwashed with saturated aqueous sodium chloride
4. dry with materialdried over anhydrous magnesium sulfate
5. filtrationfiltered
6. concentrationThe filtrate was concentrated under a reduced pressure
7. stirringwas stirred for 40 minutes at room temperature
8. temperaturewhile cooling appropriately
9. extractionwhich was then extracted with ethyl acetate
10. customThe organic layer was separated
11. washwashed with saturated aqueous sodium chloride
12. dry with materialdried over anhydrous magnesium sulfate
13. filtrationfiltered
14. concentrationThe filtrate was concentrated under a reduced pressure
15. customthe residue was purified by NH silica gel column chromatography (heptane:ethyl acetate=2:1)