Efficient Solid-Phase Synthesis of β-Aminosubstituted Piperidinols

The solid-phase synthesis of a β-aminosubstituted piperidinol library starting from 1,2,3,6-tetrahydropyridine is described. The synthetic strategy involves formation of the 3,4-epoxypiperidine Wang resin 4 and subsequent ring opening with primary and secondary amines. The epoxide ring-opening was efficiently promoted by lithium perchlorate in acetonitrile. The progress of the reaction sequences leading to the epoxide resin 4 was monitored by ATR FTIR on single resin bead and HRMAS NMR techniques. This methodology is considered to be suitable for the generation of arrays of compounds.