反应详情

Piperidin-4-yl-carbamic acid tert-butyl ester (commercially available from ASTATECH) (5 g, 24.96 mmol), 2,2,2,-trifluoroethyl trichloromethane sulfonate (7.03 g, 1 equivalent), and potassium carbonate (4.1 g, 1.2 eq) were taken up in acetone (80 mL) and heated at reflux with stirring for 17 hours. The solvent was removed under reduced pressure at 40° C. and ethyl acetate and water were added to the residue. The layers were partitioned and then separated. The organic layer was washed with water and brine, dried over magnesium sulfate, filtered, and concentrated to give a dark colored solid. Purification by chromatography on silica gel using 15% ethyl acetate in hexanes as the eluant gave [1-(2,2,2-trifluoroethyl)piperidin-4-yl]-carbamic acid tert-butyl ester (4.45 g) as an off-white powder, m.p. 99.2-99.8° C., (M+H)+=283.

1. temperatureheated
2. temperatureat reflux
3. customThe solvent was removed under reduced pressure at 40° C.
4. additionethyl acetate and water were added to the residue
5. customThe layers were partitioned
6. customseparated
7. washThe organic layer was washed with water and brine
8. dry with materialdried over magnesium sulfate
9. filtrationfiltered
10. concentrationconcentrated
11. customto give a dark colored solid
12. customPurification by chromatography on silica gel using 15% ethyl acetate in hexanes as the eluant