反应详情

1-(4-Aminobutyl)-4-methoxybenzene hydrochloride (2.0 g, 9.27 mmol) was dissolved in water (10 ml). Toluene (20 ml) and 2N-sodium hydroxide (10 ml) were added and the mixture was partitioned. The mixture was washed 20% brine (10 ml) twice, dried over anhydrous sodium sulfate and concentrated under reduced pressure. Methanol (5 ml) was added and the mixture was concentrated under reduced pressure. The residue was dissolved in methanol (10 ml). This methanol solution was added dropwise to a slurry of 2,2-dichloroacetaldehyde tosylhydrazone (5213 mg, 18.54 mmol) in methanol (30 ml) at 20-25° C. and the mixture was stirred at room temperature for 3 hours. The reaction mixture was poured into a mixture of toluene (19 ml) and saturated aqueous sodium hydrogen carbonate (57 ml) and the mixture was stirred at room temperature for 50 min. The organic solvent was evaporated by concentration under reduced pressure and the residue was extracted with toluene (40 ml). 4N-Sodium hydroxide (30 ml) was added, and the mixture was heated to 50-60° C. and partitioned. Water (30 ml) was added, and the mixture was heated to 50-60° C. and partitioned. Water (30 ml) was added, and the mixture was heated to 50-60° C. and partitioned. The organic layer was washed with 20% citric acid (15 ml), and then 3 times with water (20 ml), with saturated aqueous sodium hydrogen carbonate (30 ml) and with water (30 ml), and concentrated under reduced pressure. The residue was dissolved in ethanol (10 ml) and concentrated hydrochloric acid (2.5 ml) was added. The mixture was concentrated under reduced pressure and 2-propanol was added, and the mixture was concentrated under reduced pressure. Ethyl acetate was added, and the mixture was concentrated under reduced pressure. Ethyl acetate (10 ml) was added and triturated. The mixture was stirred at room temperature for 40 min. The precipitated crystals were collected by filtration and dried under reduced pressure to give 1-[4-(4-methoxyphenyl)butan-1-yl]-1H-1,2,3-triazole hydrochloride (1.61 g, yield 68%).

1. customthe mixture was partitioned
2. washThe mixture was washed 20% brine (10 ml) twice
3. dry with materialdried over anhydrous sodium sulfate
4. concentrationconcentrated under reduced pressure
5. additionMethanol (5 ml) was added
6. concentrationthe mixture was concentrated under reduced pressure
7. dissolutionThe residue was dissolved in methanol (10 ml)
8. stirringthe mixture was stirred at room temperature for 50 min
9. customThe organic solvent was evaporated by concentration under reduced pressure
10. extractionthe residue was extracted with toluene (40 ml)
11. addition4N-Sodium hydroxide (30 ml) was added
12. temperaturethe mixture was heated to 50-60° C.
13. custompartitioned
14. additionWater (30 ml) was added
15. temperaturethe mixture was heated to 50-60° C.
16. custompartitioned
17. additionWater (30 ml) was added
18. temperaturethe mixture was heated to 50-60° C.
19. custompartitioned
20. washThe organic layer was washed with 20% citric acid (15 ml)
21. concentration3 times with water (20 ml), with saturated aqueous sodium hydrogen carbonate (30 ml) and with water (30 ml), and concentrated under reduced pressure
22. dissolutionThe residue was dissolved in ethanol (10 ml)
23. additionconcentrated hydrochloric acid (2.5 ml) was added
24. concentrationThe mixture was concentrated under reduced pressure and 2-propanol
25. additionwas added
26. concentrationthe mixture was concentrated under reduced pressure
27. additionEthyl acetate was added
28. concentrationthe mixture was concentrated under reduced pressure
29. additionEthyl acetate (10 ml) was added
30. customtriturated
31. stirringThe mixture was stirred at room temperature for 40 min
32. filtrationThe precipitated crystals were collected by filtration
33. customdried under reduced pressure