Preparation of (R)-3-aminopiperidine by resolution with optically active cyclic phosphoric acids.

ABSTRACT

(R)-3-aminopiperidine ((R)-APD), a key intermediate for alogliptin, trelagliptin, and linagliptin, was successfully resolved from racemic 3-aminopiperidine with an enantiomerically pure resolving agent, namely, (R)-4-(2-chlohydroxy-1.3.2-dioxaphosphorinane 2-oxide ((R)-CPA), via diastereomeric salt formation. By this resolution approach, (R)-3-aminopiperidine was obtained in 99.5% yield with 99.6%e.e.