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

Yujuan Sun; Beibei Hu; Yongshuai Jing; Jialiang Wu; Maochao Zhou; Meng Chen; Feifei Hao; Chen Zhang; Fengxia Sun

doi:10.1002/chir.23312

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

Chirality. 2021 Jul;33(7):379-384. doi: 10.1002/chir.23312. Epub 2021 May 3.

Authors

Yujuan Sun^{1

2}, Beibei Hu^{1

2}, Yongshuai Jing^{1

2}, Jialiang Wu¹, Maochao Zhou¹, Meng Chen, Feifei Hao¹, Chen Zhang³, Fengxia Sun^{1

2}

Affiliations

¹ College of Chemical and Pharmaceutical Engineering, Hebei University of Science and Technology, Shijiazhuang, China.
² Research Centre for Chemical Safety and Verification of the CWC, Hebei University of Science and Technology, Shijiazhuang, China.
³ R&D Tech Centre, Hebei Chiral Chem and Biotech Co., Ltd, Shijiazhuang, China.

PMID: 33942379
DOI: 10.1002/chir.23312

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.

Keywords: (R)-3-aminopiperidine; chiral cyclic phosphoric acids; diastereomeric salt; resolution; resolving agent.

Publication types

Research Support, Non-U.S. Gov't

Abstract

Publication types

Grants and funding