Nitroethane → 1,2-Dimethoxy-4-(2-nitroprop-1-enyl)benzene

Participants

Reaction Steps

According to the present invention, (R)-3,4-dimethoxyamphetamine (3) is prepared according to the synthesis depicted in following Scheme I whereby the starting material 3,4-dimethoxy-benzaldehyde (veratric aidehyde) (10), which is a cheap raw material available from the market, is condensed with nitroethane (Henry's reaction), to form 3,4-dimethoxy-phenyl-2-nitropropene (11), which is then suitably reduced to an intermediate, i.e., 3,4-dimethoxy-phenyl-acetone (12) by means of a catalytic hydrogenation. The intermediate (12) is then reacted with an optically active amine, (R)-α-methyl-benzyl-amine (13) to form the corresponding chiral imine (14). In a key step of the present synthesis, the chiral amine (14) is diastereo-selectively reduced to the intermediate product, (R,R)-N-phenylethyl-3,4-dimethoxy-amphetamine (15) hydrochloride by catalytic hydrogenation with Raney-Nickel. The intermediate (15) is finally debenzylated by hydrogenation, to form (R)-3,4-dimethoxyamphetamine (3) hydrochloride. ##STR12##

Provenance & Evidence