Method for the production of galanthamine and its derivatives

摘要

Disclosed is a process for the production of 4a,5,9,10,11,12,-hexahydro-6H-benzofuro[3a,3,2-ef][2]benzazepine derivatives with the general formulae I and / or II, and particularly for the synthesis of galanthamine derivatives; in that the process includes the steps of: a) debrominating racemic bromine narwedine of formula (III) with palladium (II) acetate and triphenylphosphine to give te compound of formula (IV); b) the work up, and conversion of racemic narwedine (IV) into an enantiomerically pure narwedine of formula (V), wherein the reaction work up includes the step of precipitating the palladium catalyst by oxidation by sustained exposure to oxygen or a source or peroxide in the presence of activated carbon; c) reducing the enantiomerically pure narwedine to obtain enantiomerically pure galanthamine of general formula (I) with R1 equal to CH3; d) alkylation or dealkylation of galanthamine to give the compounds of general formula (I); and optionally followed by the salt formation to give the compounds of general formula (II); wherein the substituents are as defined herein.