Ethyl Acetate → 4-n-Butyl-1-[4-(2-benzyloxyphenyl)-4-oxo-1-butyl]piperidine

Participants

Reaction Conditions

Reaction Steps

In a 25 mL oven-dried flask was added Mg turnings (123 mg, 5.1 mmol) which was activated by the use of a heat-gun under vacuum. Under inert atmosphere was added a solution of 1-benzyloxy-2-iodo-benzene (25) (1.18 g, 3.8 mmol) in Et2O (10 mL) and the reaction mixture was allowed to reflux for 3.5 hours. A solution of 4-(4-n-butylpiperidin-1-yl)butanenitrile 4 (0.53 g, 2.5 mmol) dissolved in CH2Cl2 (3 mL) was added and the reaction mixture and was stirred at 40° C. over-night. The reaction mixture was quenched by addition of H2SO4 (10 mL, 2 M) and left stirring for 1 hour, followed by addition of NaOH (20 mL, 2 M) until basic conditions. The reaction mixture was extrated with ethyl acetate (3×50 mL)) and the combined organic phases are washed with brine (10 mL) and NaOH (10 mL, 2 M), and the combined organic phases were dried (MgSO4) and evaporated to dryness to produce 1.28 g of crude 26. The crude product was subjected to CC [eluent: Tol:EtOAc (1:1)] to give pure 26 (0.51 g, 51%); LC-MS [M+H]+ 393 (cald. 393.7).

Provenance & Evidence