One-pot synthesis of a new potential analgesic over bifunctional palladium/amberlyst catalysts

(−)-(2S,3S)-1-Dimethylamino-3-(3-methoxy-phenyl)-2-methyl-pentan-3-ol hydrochloride was directly dehydroxylated to the new opioidic (−)-(2R,3R)-[3-(3-methoxy-phenyl)-2-methyl-pentyl]-dimethyl-amin hydrochloride over Pd containing Amberlyst-15. The obtained product exhibits pronounced analgesic efficiency. Two reaction steps are involved in this one-pot synthesis: dehydration of the starting tertiary alcohol followed by hydrogenation of the obtained olefin (Z + E)-(S)-[3-(3-methoxy-phenyl)-2-methyl-pent-3-enyl]-dimethyl-amine hydrochloride. The dehydration of the alcohol occurs only in the presence of an Amberlyst resin as solid acid catalyst, which also serves as support for the hydrogenation component Pd. Surprisingly, only such a relatively simple well known Pd/Amberlyst system provides excellent results for this complicated one-pot conversion. Other acidic heterogeneous catalysts did not show catalytic performance for this kind of reaction. The various reaction parameters of this one-pot dehydroxylation reaction were optimized using a statistical test design program.