反应详情

温度

105 °C

To an acetic acid (5.00 mL) solution of 6-(4-fluoro-phenoxymethyl)-pyridine-3-carbaldehyde (500 mg, 1.30 mmol) described in Manufacturing Example 72-1-2 were added nitromethane (923 mg, 15.1 mmol) and ammonium acetate (333 mg, 4.32 mmol) under nitrogen atmosphere, which was stirred for 2 hours at 105° C. Water and ethyl acetate were added to the reaction mixture, and the organic layer was extracted with ethyl acetate. The organic layer was washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The solvent was evaporated from the filtrate under a reduced pressure. Dimethyl sulfoxide (10.0 mL) and acetic acid (600 μL) were added to the residue, and sodium borohydride (131 mg, 3.46 mmol) was then added at room temperature while cooling appropriately. Following 20 minutes of stirring, water was added dropwise at room temperature while cooling appropriately. The reaction mixture was extracted with ethyl acetate, and the organic layer was washed with water 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 NH silica gel column chromatography (ethyl acetate:heptane=1:1) to obtain the title compound (50 mg, 8.38%).

1. extractionthe organic layer was extracted with ethyl acetate
2. washThe organic layer was washed with water and saturated aqueous sodium chloride
3. dry with materialdried over anhydrous magnesium sulfate
4. filtrationfiltered
5. customThe solvent was evaporated from the filtrate under a reduced pressure
6. additionwas then added at room temperature
7. temperaturewhile cooling appropriately
8. waitFollowing 20 minutes
9. stirringof stirring
10. temperaturewhile cooling appropriately
11. extractionThe reaction mixture was extracted with ethyl acetate
12. washthe organic layer was washed with water and saturated aqueous sodium chloride
13. dry with materialdried over anhydrous magnesium sulfate
14. filtrationfiltered
15. concentrationThe filtrate was concentrated under a reduced pressure
16. customthe residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=1:1)