1-苄基-3-甲基哌啶-4-酮

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:-50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of n-butyllithium (1-2 equivalents, preferably 1.1 equivalents) (1.6 M in hexane, 8.6 ml, 13.76 mmol) in Et2O (10.32 mL) was added a solution of 1-bromo-4-fluorobenzene (2.21 g, 12.63 mmol) in Et2O (5 ml) at about −50° C. After the reaction mixture was stirred at about −50° C. for about 40 min, a solution of 1-benzyl-3-methylpiperidin-4-one (2.00 g, 9.84 mmol) in Et2O (7 mL) was added dropwise. The mixture was allowed to warm up to about −20° C. to 0° C. (preferably −10° C.). 1M hydrochloric acid (20 mL) was added and the organic phase was discarded. Et2O (20 mL) was added to the aqueous solution and aqueous NH4OH was added to the solution until pH>9. The organic layer was separated and the aqueous layer was extracted with DCM (20 mL), The combined organic portions were washed with brine (2×10 mL), dried over MgSO4, filtered, and concentrated in vacuo to give 1-benzyl-4-(4-fluorophenyl)-3-methylpiperidin-4-ol (2.48 g, 84%) as an oil which was used in subsequent reactions without further purification. RP-HPLC (Table 1, Method a) Rt 1.63 min; m/z: (M+H)+ 300. to warm up to about −20° C. to 0° C. (preferably −10° C.) was added to the solution until pH>9 The organic layer was separated the aqueous layer was extracted with DCM (20 mL) The combined organic portions were washed with brine (2×10 mL) dried over MgSO4 filtered concentrated in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Dry tetrahydrofuran (20 ml) was added to a stirred mixture of 1-benzyl-3-methylpiperidin-4-one (4 g, 19.7 mmole) and (Trifluoromethyl) trimethylsilane (3.35 g, 23.64 mmole) at 0° C. and stirred for 5 min. Tetrabutyl ammonium fluoride (0.05 g) was added to it at 0° C. and stirred for another 30 min at 0° C. The reaction mixture was allowed to warm to room temperature, stirred for 3 hr, acidified with 2N HCl to pH 2 and extracted with ether (3×50 ml). Ether extract was dried (Na2SO4) and concentrated in vacuum to give 1-benzyl-3-methyl-4-hydroxy-4-trifluoromethylpiperidine. Yield 5.1 g (95%), C14H18F3NO, m/z 274 (M+1). stirred for another 30 min at 0° C stirred for 3 hr extracted with ether (3×50 ml) Ether extract was dried (Na2SO4) concentrated in vacuum