Water → N-alpha-phenyl-ethyl-3,4-dimethoxy-amphetamine

Participants

Reaction Steps

Said synthesis was developed by D. E. Nichols et al. ("J. Med. Chem.", 1973, 16, 480-48 and U.S. Pat. No. 4,000,197, of 12.28.1976) and was applied to the chiral synthesis of several methoxylated amphetamines, including (S)-3,4-dimethoxy-amphetamine, which is an enantiomer of (3). In U.S. Pat. No. 4,000,197, the synthesis of the iminic intermediate is carried out in benzene under refluxing conditions during 24 hours with formed water being simultaneously azeotroped off; the hydrogenation is carried out with Raney-Nickel as the catalyst, in absolute ethanol under medium-pressure hydrogen (3 atm of H2). The N-α-phenyl-ethyl-3,4-dimethoxy-amphetamine (15) intermediate is isolated as hydrochloride salt, by crystallization in aqueous acetone or acetone/isopropanol blend, in moderate yield (relatively to dimethoxy-phenyl-acetone), of 48%.

Provenance & Evidence