| abstract |
N-substituted -14-hydroxy-3-substituted-morphinan derivatives have been found to possess potent narcotic agonist or antagonist activity. In particular, the compound N-Cyclo-butylmethyl-3,14-dihydroxymorpinan has been found to possess potent agonist/antagonist activity as a non-narcotic analgesic. An improved total synthesis of these compounds is described herein from the starting material 2-(p-methoxybenzyl)-1,2,3,4, 5,6,7,8-octahydroisoquinoline. A preferred feature of the process involves borane reduction of 2-cyclobutylcarbonyl-9,10-dihydroxy-1-(p-methoxybenzyl) perhydroisoquinoline (Va) to provide the corresponding cyclobutylmethyl derivative complexed with borane which is converted directly to N-cyclobutylmethyl-14.beta.-hydroxy-3-methoxymorphinan (LVa) by treating with acid. |