反应详情

温度

80 °C

To a solution of 4-(p-tolyl)aminopiperidine trifluoroacetate (2.08 g) and (3-bromopropenyl)-2-nitrobenzene (3.01 g) dissolved in N,N-dimethylformamide (20 mL) was added potassium carbonate (2.75 g). The solution was stirred with heating at 80° C. for 2 hours. Dichloromethane was added to the reaction solution and the insolubles were filtered off, and the solvent was distilled off under reduced pressure. The resulting residue was purified by chromatography [silica gel, dichloromethane-methanol-aqueous ammonia (95:5:0.3)] to give a yellow oily substance (1.05 g). This was dissolved in acetic acid (25 mL), to which 10% palladium carbon (0.50 g) was added. The mixture was vigorously stirred at room temperature under hydrogen atmosphere for 1 hour. The catalyst was filtered off and the solvent was distilled off under reduced pressure. The resulting residue was purified by chromatography [silica gel, dichloromethane-methanol-aqueous ammonia (90:10:0.5)] to give a brown oily substance (0.5443 g). Part of the substance (0.3870 g), cyclohexaneacetic acid (0.28 g), 4-dimethylaminopyridine (0.50 g) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.46 g) were dissolved in N,N-dimethylformamide (5 mL). The solution was stirred at room temperature for 18 hours. After addition of ethyl acetate, the solution was washed in turn with saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution, dried (MgSO4), and the solvent was distilled off under reduced pressure. The resulting residue was purified by chromatography [silica gel, dichloro-methane-methanol-aqueous ammonia (97:3:0.2)] to give the title compound (0.4190 g).

1. filtrationthe insolubles were filtered off
2. distillationthe solvent was distilled off under reduced pressure
3. customThe resulting residue was purified by chromatography [silica gel, dichloromethane-methanol-aqueous ammonia (95:5:0.3)]
4. customto give a yellow oily substance (1.05 g)
5. additionwas added
6. stirringThe mixture was vigorously stirred at room temperature under hydrogen atmosphere for 1 hour
7. filtrationThe catalyst was filtered off
8. distillationthe solvent was distilled off under reduced pressure
9. customThe resulting residue was purified by chromatography [silica gel, dichloromethane-methanol-aqueous ammonia (90:10:0.5)]
10. customto give a brown oily substance (0.5443 g)
11. stirringThe solution was stirred at room temperature for 18 hours
12. washthe solution was washed in turn with saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution
13. dry with materialdried (MgSO4)
14. distillationthe solvent was distilled off under reduced pressure
15. customThe resulting residue was purified by chromatography [silica gel, dichloro-methane-methanol-aqueous ammonia (97:3:0.2)]