85284-04-4

Upstream product

• 16676-33-8 (4R,4aS,7aR,12bS)-3-(cyclobutylmethyl)-4a,9-dihydroxy-2,3,4,4a,5,6-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-7(7aH)-one 
• 52446-24-9 (-)-4,5α-epoxy-3,14-dihydroxymorphinan-6-one hydrochloride 
• 33522-95-1 noroxymorphone 

Relevant academic research and scientific papers

One-Pot Process for Synthesis of Nalbuphine Hydrochloride and Impurity Control Strategy

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.

Preparation method of nalbuphine free alkali

The invention discloses a preparation method of nalbuphine free alkali, i.e., (-)-17-(cyclobutylmethyl)-4,5alpha-epoxymorphine-3,6alpha,14-hydroxyl. A synthetic route of the preparation method is shown in the specification. According to the novel method, a new reduction reaction condition is adopted, so the purity of nalbuphine free alkali in a reduction product reaches 99%, and the problems of excessive generation of 6-beta isomers of the reduction product and difficulty in purification of the free alkali are avoided.