反应详情

温度

45 °C

1-(Cyclohex-1-en-1-ylmethyl)piperidin-4-amine obtained in Example 4b (240 mg, 1.24 mmol), N,N-dimethylformamide (3 ml), triethylamine (344 μl, 2.47 mmol) and PyBOP (856 mg, 1.64 mmol) were added to (3R*,4S*)-3-[2-(tert-butoxy)-2-oxoethyl]-4-methylpyrrolidine-3-carboxylic acid obtained in Example 4h (200 mg, 0.822 mmol), followed by stirring with heating in a 45° C. oil bath for 1.5 hours. Water was added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated. 2-(Bromomethyl)-1-chloro-3-(trifluoromethyl)benzene (247 mg, 0.903 mmol), potassium carbonate (170 mg, 1.23 mmol) and N,N-dimethylformamide (1 ml) were added thereto, followed by heating with stirring in a 45° C. oil bath for three hours. Water was added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed with water and brine and then dried over magnesium sulfate. The resulting crude product was purified by column chromatography twice (NH silica gel, elution solvent: ethyl acetate/heptane and silica gel, elution solvent: ethyl acetate/heptane) to give the title compound (353 mg, yield 70.1%).

1. extractionwas extracted with ethyl acetate
2. dry with materialThe organic layer was dried over magnesium sulfate
3. concentrationconcentrated
4. temperatureby heating
5. stirringwith stirring in a 45° C. oil bath for three hours
6. extractionwas extracted with ethyl acetate
7. washThe organic layer was washed with water and brine
8. dry with materialdried over magnesium sulfate
9. customThe resulting crude product was purified by column chromatography twice (NH silica gel, elution solvent: ethyl acetate/heptane and silica gel, elution solvent: ethyl acetate/heptane)