tert-butyl N-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]carbamate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Into a 50-mL round-bottom flask, was placed tert-butyl N-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]carbamate (2.0 g, 7.08 mmol, 1.00 equip), dichloromethane (20 mL), and CF3COOH (4 mL). The resulting solution was stirred overnight at room temperature. The resulting mixture was concentrated under vacuum to yield 1-(2,2,2-trifluoroethyl)piperidin-4-amine 2,2,2-trifluoroacetate as a yellow oil. (ES, m/z) 183 [M+H]+ Into a 50-mL round-bottom flask, was placed The resulting mixture was concentrated under vacuum

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Into a 50-mL 3-necked round-bottom flask, was placed tert-butyl N-(piperidin-4-yl)carbamate (2 g, 9.99 mmol, 1.00 equip), tetrahydrofuran (20 mL), To this was added sodium hydride (480 mg, 20.00 mmol, 2.00 equip) at 0° C. The resulting solution was stirred for 0.5 h at 0° C., and 2,2,2-trifluoroethyl trifluoromethanesulfonate (2.784 g, 11.99 mmol, 1.20 equip) was added. The resulting solution was stirred for 2 h at 0° C. The reaction was then quenched by the addition of water (100 mL). The resulting solution was extracted with ethyl acetate (3×50 mL) and the organic layers combined and dried over anhydrous sodium sulfate. The solids were filtered out. The filtrate was concentrated under vacuum to yield tert-butyl N-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]carbamate as yellow oil. LCMS (ES, m/z) 283 [M+H]+ Into a 50-mL 3-necked round-bottom flask, was placed The resulting solution was stirred for 2 h at 0° C The reaction was then quenched by the addition of water (100 mL) The resulting solution was extracted with ethyl acetate (3×50 mL) dried over anhydrous sodium sulfate The solids were filtered out The filtrate was concentrated under vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A suspension of 1.26 g (0.0045 mole) of [1-(2,2,2-trifluoro-ethyl)-piperidin-4-yl]-carbamic acid tert-butyl ester in 10 mL of 4 M HCl in dioxane solution was stirred at room temperature for 24 hours. Volatiles were removed under reduced pressure, methanol was added to the residue followed by ether. The resulting solid was collected by filtration, washing with ether to give 0.92 g of 1-(2,2,2-trifluoro-ethyl)-piperidin-4-ylamine; hydrochloride as a white solid. Volatiles were removed under reduced pressure, methanol was added to the residue The resulting solid was collected by filtration washing with ether

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: [1-(2,2,2-Trifluoroethyl)piperidin-4-yl]-carbamic acid tert-butyl ester was then taken up in dioxane (80 mL) and hydrogen chloride gas was bubbled through the solution for 10 minutes. The reaction vessel was capped tightly and stirred for 1.5 hours. The solvent was removed under reduced pressure at 40° C. The residue was taken up in 42 mL of 0.5M sodium methoxide in methanol, stirred at room temperature for 3 hours, and filtered. The filtrate was concentrated, taken up in ethyl acetate, filtered, and concentrated to give 1.0 g of 1-(2,2,2-trifluoroethyl)piperidin-4-ylamine as a dark colored oil, (M+H)+=183. hydrogen chloride gas was bubbled through the solution for 10 minutes The reaction vessel was capped tightly The solvent was removed under reduced pressure at 40° C stirred at room temperature for 3 hours filtered The filtrate was concentrated filtered concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 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. heated at reflux The solvent was removed under reduced pressure at 40° C. ethyl acetate and water were added to the residue The layers were partitioned separated The organic layer was washed with water and brine dried over magnesium sulfate filtered concentrated to give a dark colored solid Purification by chromatography on silica gel using 15% ethyl acetate in hexanes as the eluant