16676-33-8Relevant articles and documents
One-Pot Process for Synthesis of Nalbuphine Hydrochloride and Impurity Control Strategy
Chen, Yibo,Wu, Zenong,Yang, Zhezhou,Zhang, Fuli,Zhang, Tao,Zhao, Weili
, p. 1707 - 1717 (2020/12/01)
An improved kilogram-scale process of synthesis of nalbuphine was developed by investigating the critical parameters. Ten process-related impurities were identified, of which the source and control strategy was elucidated. Moreover, tetramethylammonium triacetoxyborohydride (Me4NBH(OAc)3) was developed to reduce the imine and ketone in one pot. As a result, 6-β-epimer was significantly controlled to only 0.08% in the crude nalbuphine. The improved process was robust at kilogram scale in 60.4% overall yield with 99.95% high-performance liquid chromatography (HPLC) purity.