79499-59-5Relevant academic research and scientific papers
Process for (S)-Ketamine and (S)-Norketamine via Resolution Combined with Racemization
Gao, Shenghua,Gao, Xuezhi,Wu, Zenong,Li, Houyong,Yang, Zhezhou,Zhang, Fuli
supporting information, p. 8656 - 8664 (2020/07/21)
A concise, recyclable, and efficient process is presented for the preparation of (S)-ketamine (esketamine, (S)-1a) via classic resolution combined with the recycling of the undesired isomer. With commercially available ketone 2 as the starting material, this procedure features three steps including (1) an unique hydroxylation-ring expansion rearrangement, (2) mild amination via methanesulfonate, and (3) chiral separation using L-(+)-tartaric acid. The three simple steps are all performed in mild conditions and (S)-1a tartrate is obtained in 99.5percent ee without recrystallization. Subsequently, racemization of the unwanted (R)-1a remained in resolution mother liquor was performed in the presence of a Lewis acid in quantitative yield with >99.0percent chemical purity. This original and economical process afforded esketamine in 67.4percent (28.9percent without racemization) overall yield with two times recycling of the mother liquor without column purification. In addition, this procedure can also be applied to the preparation of (S)-norketamine, which is a safer potential antidepressant.
