General Method of Synthesis for Naloxone, Naltrexone, Nalbuphone, and Nalbuphine by the Reaction of Grignard Reagents with an Oxazolidine Derived from Oxymorphone

The N‐oxide of O‐acyloxymorphone, when treated with the Burgess reagent, provides the corresponding oxazolidine in a one‐pot sequence and in excellent yield. The oxazolidine derived from oxymorphone, temporarily protected at O‐3 and C‐6, reacts with Grignard reagents to provide directly N‐allyl, N‐cyclopropylmethyl, and N‐cyclobutylmethyl derivatives that are further converted to the title compounds, namely naltrexone, naloxone, nalbuphone, and nalbuphine in excellent yields. Each of these medicinal agents is obtained from the oxazolidine in a one‐pot sequence. Complete spectral and experimental data are provided for all compounds.