Isolation and synthesis of 2-chloro-10-α-hydroxynaltrexone, a new naltrexone degradant

The putative structure of a new degradant from REVIA® tablets was assigned 2-chloro-10-α-hydroxynaltrexone 2. A route for the independent synthesis was developed wherein a N,N-diethylcarbamate derivative directed an ortho-metallation of the naltrexone nucleus, leading to the desired 2-chloro functionality. Oxidation of the 10-position, followed by deprotection provided 2, which was identical in all respects to the original isolate.