反应详情

A mixture of 5-phenoxy-pyridine-2-carbaldehyde (700 mg, 3.5 mmol) described in Manufacturing Example 121-1-3, lithium methoxide (170 mg, 4.6 mmol), nitromethane (280 mg, 4.6 mmol), and methanol (10 mL) was dissolved by irradiating ultrasonic wave for 2 minutes at room temperature, after which the reaction solution was concentrated under a reduced pressure. Acetic anhydride (30 mL) and triethylamine (1.1 g, 11 mmol) were added to the residue, which was stirred for 10 minutes at room temperature, after which the reaction solution was concentrated under a reduced pressure. Ethyl acetate was added to the residue, and the organic layer was separated and washed with saturated aqueous sodium chloride once and then dried over anhydrous magnesium sulfate. The solvent was evaporated under a reduced pressure, dimethyl sulfoxide (5.0 mL), acetic acid (0.50 mL), and sodium borohydride (270 mg, 7.0 mmol) were added to the residue, which was stirred for 5 minutes at room temperature. Water and ethyl acetate were added to the reaction solution, and then the ethyl acetate layer was separated and washed with aqueous sodium bicarbonate, water, and saturated aqueous sodium chloride. The solvent was evaporated under a reduced pressure, and the residue was purified first by silica gel column chromatography (heptane: ethyl acetate=2:1) and then NH silica gel column chromatography (heptane: ethyl acetate=4:1 then 2:1) to obtain the title compound (76 mg, 8.9%).

1. dissolutionwas dissolved
2. customby irradiating ultrasonic wave for 2 minutes at room temperature
3. concentrationafter which the reaction solution was concentrated under a reduced pressure
4. concentrationafter which the reaction solution was concentrated under a reduced pressure
5. additionEthyl acetate was added to the residue
6. customthe organic layer was separated
7. washwashed with saturated aqueous sodium chloride once
8. dry with materialdried over anhydrous magnesium sulfate
9. additionwere added to the residue, which
10. stirringwas stirred for 5 minutes at room temperature
11. customthe ethyl acetate layer was separated
12. washwashed with aqueous sodium bicarbonate, water, and saturated aqueous sodium chloride
13. customThe solvent was evaporated under a reduced pressure
14. customthe residue was purified first by silica gel column chromatography (heptane: ethyl acetate=2:1)