The invention discloses a preparation method of
dextromethorphan ((+)-3-methoxy-17-methyl-(9 alpha,13 alpha,14 alpha)-levorphane, I). The method comprises the following steps that a
dextromethorphan intermediate (+)-1-(4-methoxy) benzyl-1,2,3,4,5,6,7,8-octahydro-
isoquinoline (II) conducts N-benzylation reaction with a benzylation
reagent under alkaline conditions to form (+)-1-(4-methoxy) benzyl-N-benzyl-1,2,3,4,5,6,7,8-octahydro-
isoquinoline (III); the intermediate (III) is subjected to acid cyclization reaction to form (+)-3-hydroxy-17-benzyl-(9 alpha,13 alpha,14 alpha)-levorphane, (IV); the intermediate (IV) reacts with
dimethyl sulfate or methine
halide, and is subjected to O-
methylation and N-
methylation reaction to form (+)-3-methoxy group-17-benzyl-17-methyl-(9 alpha,13 alpha,14 alpha)-levorphane
quaternary ammonium salt (V); (V) is subjected to
catalytic hydrogenation reaction; benzyl is removed; and
dextromethorphan (I) is obtained. Therefore, the preparation method can use a common and cheap
methylation reagent to substitute an unusual methylation
reagent such as phenyltrimethylammonium
hydroxide, and the yield of reaction can be increased.