反应详情

温度

25 °C

N-Methyl-N-phenyl-2,3-dihydro-1H-pyrrolizine-1-carboxamide (115.35 g, 480 mmol) and toluene (100 mL) were added to a mixture of benzoylpiperidine (95.4 g, 1.05 equivalents) and phosphorus oxychloride (88 mL, 147 g, 0.96 equivalents), which had been stirred at 25° C. for 1 hour. An additional 100 mL toluene was added. The suspension was heated to a temperature of 40° C. to 45° C. for 4 hours. The resulting syrup was transferred into a rapidly stirring solution of sodium hydroxide (180 g, 4.5 mol), piperidine (1.0 mL), and water (650 mL). The temperature was maintained at 25° C. to 35° C. and the mixture was stirred for 1 hour. A mixture of toluene (100 mL), water (50 mL), and sodium hydroxide (12 g, 300 mmol) was added to the reaction flask, and the entire reaction mixture was stirred at 25° C. for 1 hour. The suspension was then heated to 75° C. and the layers were separated. The organic layer was cooled to 60° C. and hexane (100 mL) was slowly added, and the solution slowly stirred and cooled to −15° C. The precipitate was filtered, washed with toluene/hexane (150 mL, 2:1 v/v) and then with hexane (150 mL), and dried under vacuum at 25° C. to yield 5-benzoyl-N-methyl-N-phenyl-2,3-dihydro-1H-pyrrolizine-1-carboxamide (138.01 g, 83.5% yield).

1. temperatureThe suspension was heated to a temperature of 40° C. to 45° C. for 4 hours
2. temperatureThe temperature was maintained at 25° C. to 35° C.
3. stirringthe mixture was stirred for 1 hour
4. additionwas added to the reaction flask
5. customthe entire reaction mixture
6. stirringwas stirred at 25° C. for 1 hour
7. temperatureThe suspension was then heated to 75° C.
8. customthe layers were separated
9. temperatureThe organic layer was cooled to 60° C.
10. additionhexane (100 mL) was slowly added
11. stirringthe solution slowly stirred
12. temperaturecooled to −15° C
13. filtrationThe precipitate was filtered
14. washwashed with toluene/hexane (150 mL, 2:1 v/v)
15. dry with materialwith hexane (150 mL), and dried under vacuum at 25° C.