反应详情

温度

70 °C

To a solution of (3R*,4R*)-3,4-epoxy-2,2-dimethyl-7-nitro-3-chromanol (2.07 g, 9.37 mmol) in dioxane (4 mL), lithium perchlorate (997 mg, 9.37 mmol) and 4-fluorophenethyl amine (1.47 mL, 11.3 mmol) were added, and the resulting solution was stirred at 70° C. for 3.5 hours under nitrogen atmosphere. The reaction solution was diluted with ethyl acetate, washed with saturated sodium hydrogen carbonate solution and saturated sodium chloride solution. Then, the organic phase was dried over magnesium sulfate and concentrated under a reduced pressure. The resulting residue was diluted with ethanol, and a solution of maleic acid (1.20 g, 10.3 mmol) in ethanol was added dropwise thereto. The resulting solid was filtered off, and washed with ethyl acetate. The resulting solid was suspended in ethyl acetate, the resulting suspension was neutralized with 1 mol/L sodium hydroxide aqueous solution and washed with saturated sodium chloride solution. After drying the organic phase over magnesium sulfate, it was dried under a reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1) to obtain (3R*,4S*)-4-{[2-(4-fluorophenyl)ethyl]amino}-2,2-dimethyl-7-nitro-3-chromanol (yield: 81%).

1. washwashed with saturated sodium hydrogen carbonate solution and saturated sodium chloride solution
2. dry with materialThen, the organic phase was dried over magnesium sulfate
3. concentrationconcentrated under a reduced pressure
4. additionThe resulting residue was diluted with ethanol
5. filtrationThe resulting solid was filtered off
6. washwashed with ethyl acetate
7. washwashed with saturated sodium chloride solution
8. dry with materialAfter drying the organic phase over magnesium sulfate, it
9. customwas dried under a reduced pressure
10. customThe resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1)