Acetic Acid → N-acetyl-4-(2-ethoxy-2-phenyl-n-propoxy)piperidine

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Reaction Steps

N-Acetyl-4-(2-phenylallyloxy)piperidine (7.0 g.) (prepared as in Example BB) in ethanol (10 ml.) was added to a stirred suspension of mercuric acetate (9.2 g.) in ethanol (50 ml.) at room temperature. The mixture was stirred at room temperature for one hour then cooled to 0° C. Sodium hydroxide solution (20 ml., 5 N) followed by sodium borohydride (1.03 g.) in sodium hydroxide solution (20 ml., 5 N) were added to the stirred suspension and after 10 minutes glacial acetic acid was added to pH 6. The suspension was filtered, the filtrate concentrated and the residue partitioned between chloroform and water. The organic layer was dried (Na2SO4) and the solvent evaporated in vacuo. Gas-liquid chromatographic (GLC) analysis of the product indicated incomplete conversion to the desired product therefore the oxymercuration process was repeated as above to give N-acetyl-4-(2-ethoxy-2-phenyl-n-propoxy)piperidine (7.4 g.), 84% pure by GLC. The product in ethanol (100 ml.) and sodium hydroxide solution (30 ml.) was heated under reflux for 11 hours. The organic solvent was evaporated and the aqueous solution was extracted with chloroform (3×30 ml.). The combined chloroform extracts were dried (Na2SO4) and the solvent evaporated in vacuo to give 4-(2-ethoxy-2-phenyl-n-propoxy)piperidine as an oil (3.8 g.). A sample was converted to the oxalate salt which was recrystallized twice from ethyl acetate then acetone and had an m.p. of 126°-127° C.

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