tert-Butyl methyl(3-oxopropyl)carbamate → Tert-butyl 3-(4-(dimethylamino)-4-phenylpiperidin-1-yl)propyl(methyl)carbamate

Participants

Reaction Conditions

Reaction Steps

11.1 g (1.3 eq.) tert-butyl methyl(3-oxopropyl)carbamate were added to a solution of 11 g (1 eq.) N,N-dimethyl-4-phenylpiperidin-4-amine dihydrochloride in 110 ml methanol at 0° C. and the reaction mixture was stirred for 15 min at 0° C. 6.2 g (3 eq.) sodium cyanoboron hydride were then added in portions and the mixture was stirred for 30 min at room temperature. The reaction mixture obtained was adjusted to a pH of 5-6 with acetic acid and stirred for 12 h at room temperature. The reaction course was monitored by thin-layer chromatography (20% MeOH/CHCl3). As the conversion was still not complete, 2.4 g sodium cyanoboron hydride were added and the reaction mixture obtained was adjusted to pH 5-6 with acetic acid and stirred for 60 min at room temperature. Once the conversion was complete, the methanol was distilled off, the mixture was made alkaline with saturated NaHCO3 solution, the mixture obtained was extracted with chloroform (3×100 ml) and the combined organic phases were dried over Na2SO4. Following removal of the solvent under reduced pressure, the residue was purified by column chromatography (silica gel; 5% MeOH/CHCl3). 9 g (60%) of product were obtained.

Provenance & Evidence