Preparation of (R)‐3‐aminopiperidine by resolution with optically active cyclic phosphoric acids. Issue 7 (3rd May 2021)

• Record Type: Journal Article
• Authors: Sun, Yujuan; Hu, Beibei; Jing, Yongshuai; Wu, Jialiang; Zhou, Maochao; Chen, Meng; Hao, Feifei; Zhang, Chen; Sun, Fengxia
• Is Part Of: Chirality. Volume 33:Issue 7(2021)
• Page Start: 379
• Page End: 384
• Publication Date: 2021-05-03
• Subjects: chiral cyclic phosphoric acids -- diastereomeric salt -- resolution -- resolving agent -- (R)‐3‐aminopiperidine; Chirality -- Periodicals; Pharmaceutical chemistry -- Periodicals; 541.22
• DOI: 10.1002/chir.23312
• Languages: English
• ISSNs: 0899-0042

Abstract

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 . Abstract : Racemic APD was reacted with the resolving agent, namely, ( R )‐CPA, to obtain two diastereoisomers. They can be separated by resolution for their large difference in solubility in 90% tert ‐butyl alcohol (TBA) at 0°C. Subsequently, ( R )‐APD, an important intermediate, was yielded.