PROCESSES FOR PREPARING MORPHINANS AND INTERMEDIATES THEREOF

摘要

The present invention is directed to processes for the synthesis of morphinans. In particular, a process for cyclizing a ß,?-bicyclic ketone compound to form a nordihydrothebainone product using the Grewe cyclization reaction is improved by forming a reaction mixture comprising a ß,?-bicyclic ketone compound, a cyclizing acid and a water scavenging cyclization additive. In one embodiment, the Grewe transformation occurs in the presence of an acid anhydride as the cyclization additive. Further, the present invention is directed to processes for converting a,ß-bicyclic ketone compounds (e.g., by-products of the Grewe cyclization reaction) to ß,?-bicyclic ketone compounds, wherein the ß,?-bicyclic ketone compounds may be recovered to further undergo Grewe cyclization and form the nordihydrothebainone product.