Electrochemical N-Demethylation of 14-Hydroxy Morphinans: Sustainable Access to Opioid Antagonists
Electrochemical N-Demethylation of 14-Hydroxy Morphinans: Sustainable Access to Opioid Antagonists
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DOI：
10.1021/acs.orglett.0c02424
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发表时间：
2020-09-04
期刊：
影响因子：
5.2
通讯作者：
Cantillo, David
中科院分区：
文献类型：
--
作者：
Glotz, Gabriel;Kappe, C. Oliver;Cantillo, David
在许多阿片类拮抗剂的制备过程中，最具挑战性的步骤是对14-羟基吗啡前体进行选择性N-脱甲基。这一过程是使用化学计量的危险化学品大规模进行的，如氰化物、溴化物或氯甲酸盐。在叔胺阳极氧化的基础上，我们开发了一种温和的、无试剂和催化剂的N-脱甲基步骤。随后的中间体可以很容易地以非常好的产率被水解成目标非阿片类药物。
The most challenging step in the preparation of many opioid antagonists is the selective N-demethylation of a 14-hydroxymorphinan precursor. This process is carried out on a large scale using stoichiometric amounts of hazardous chemicals like cyanogen bromide or chloroformates. We have developed a mild reagent- and catalyst-free procedure for the N-demethylation step based on the anodic oxidation of the tertiary amine. The ensuing intermediates can be readily hydrolyzed to the target nor-opioids in very good yields.