反应详情

温度

100 °C

(R)-1-[4-(2,3-epoxy-2-methylpropoxy)phenyl]-4-[4-(trifluoromethoxy)phenoxy]piperidine (10.0 g, 23.6 mmol, optical purity of 94.3% ee), 2-chloro-4-nitroimidazole (4.0 g, 27.2 mmol), sodium acetate (0.4 g, 4.9 mmol), and t-butyl acetate (10 ml) were mixed and stirred at 100° C. for 3.5 hours. Methanol (70 ml) was added to the reaction mixture, and then a 25% sodium hydroxide aqueous solution (6.3 g, 39.4 mmol) was added thereto dropwise while cooling with ice. The resulting mixture was stirred at 0° C. for 1.5 hours, and further stirred at approximately room temperature for 40 minutes. Water (15 ml) and ethyl acetate (5 ml) were added thereto, and the mixture was stirred at 45 to 55° C. for 1 hour. The mixture was cooled to room temperature, and the precipitated crystals were collected by filtration. The precipitated crystals were subsequently washed with methanol (30 ml) and water (40 ml). Methanol (100 ml) was added to the resulting crystals, followed by stirring under reflux for 30 minutes. The mixture was cooled to room temperature. The crystals were then collected by filtration and washed with methanol (30 ml). The resulting crystals were dried under reduced pressure, obtaining 9.3 g of the objective product (yield: 73%).

1. temperaturedropwise while cooling with ice
2. stirringThe resulting mixture was stirred at 0° C. for 1.5 hours
3. stirringfurther stirred at approximately room temperature for 40 minutes
4. stirringthe mixture was stirred at 45 to 55° C. for 1 hour
5. temperatureThe mixture was cooled to room temperature
6. filtrationthe precipitated crystals were collected by filtration
7. washThe precipitated crystals were subsequently washed with methanol (30 ml) and water (40 ml)
8. additionMethanol (100 ml) was added to the resulting crystals
9. stirringby stirring
10. temperatureunder reflux for 30 minutes
11. temperatureThe mixture was cooled to room temperature
12. filtrationThe crystals were then collected by filtration
13. washwashed with methanol (30 ml)
14. customThe resulting crystals were dried under reduced pressure