反应详情

A mixture of N-trityl-3-piperidone (1.22 g, 3.6 mmol), magnesium sulfate (2.70 g) and pyrrolidine (0.36 mL, 4.3 mmol) in 10 mL of tetrahydrofuran was stirred at room temperature for 72 h. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The resultant crude enamine was dissolved in 13 mL of dry dioxane, cooled to approximately 10° C. and treated dropwise with 4-ethoxy-1,1,1-trifluoro-3-buten-2-one (0.61 mL, 4.3 mmol). The resultant orange solution was allowed to warm to room temperature overnight. Ammonium acetate (0.60 g) was added to the blood-red solution, and the mixture was heated at reflux for 2.5 h, cooled to room temperature and concentrated under reduced pressure. The residue was stirred with 100 mL of dry ether, filtered through a pad of Celite, and concentrated under reduced pressure. The resultant dark red gum was purified by flash chromatography (silica gel; 3% ethyl acetate/hexanes as eluant) to afford impure product. A portion (147 mg) of this material was further purified by preparative TLC (silica gel; 5% ethyl acetate/hexanes as eluant) to afford the title compound as a light yellow foam. LC/MS 365.2 (M+1).

1. filtrationThe reaction mixture was filtered
2. concentrationthe filtrate was concentrated under reduced pressure
3. dissolutionThe resultant crude enamine was dissolved in 13 mL of dry dioxane
4. temperaturecooled to approximately 10° C.
5. temperatureto warm to room temperature overnight
6. temperaturethe mixture was heated
7. temperatureat reflux for 2.5 h
8. temperaturecooled to room temperature
9. concentrationconcentrated under reduced pressure
10. stirringThe residue was stirred with 100 mL of dry ether
11. filtrationfiltered through a pad of Celite
12. concentrationconcentrated under reduced pressure
13. customThe resultant dark red gum was purified by flash chromatography (silica gel; 3% ethyl acetate/hexanes as eluant)
14. customto afford impure product
15. customA portion (147 mg) of this material was further purified by preparative TLC (silica gel; 5% ethyl acetate/hexanes as eluant)