Study On The Synthetic Improvement Of (R)-3-aminopiperidine Dihydrochloride

(R)-3-aminopiperidine dihydrochloride is an important medicine intermediate as dipeptidyl peptidaseâ…£(DPP-â…£) inhibitors. In this paper, (R)-3-aminopiperidine dihydrochloride was synthesized from D-glutaminic acid in 9 steps. Initial esterization and amino protection with Cbz, followed by reduction of ester group with NaBH4, activation of hydroxyl group by the formation of methanesulfonate, cylization with benzyl amine to obtain piperidine scafford, subsequential amino group deprotection of Cbz and reprotection with Boc, and final hydrogenolysis with Pd/C and hydrolysis with SOCl2, afforded the target molecule in total 37.7% yield. The structure of final molecule was determined by 1H NMR. The reaction process was monitored by HPLC or GC. This route, avoiding the chiral resolutions with satisfactory yield and mild reaction conditions, is an ideal industrial synthetic route.