合成路线1

Condensation of methyl 3-(3-hydroxyphenyl)propanoate (I) with an excess of methyl magnesium bromide in THF at low temperature afforded tertiary alcohol (II), which was brominated with N-bromosuccinimide (NBS) in DMF at 0 C to give (III). Then, a double Mannich reaction with pyrrolidine (IV) and formaldehyde provided diamine (V). To hydrogenolyze the benzylic amine groups an indirect route was required. Thus, reaction with an excess of 4-methoxybenzylmercaptan (VI) at 180 C displaced both amino groups with concomitant debromination to give thioether (VII), which was desulfurized on treatment with Raney Nickel to the dimethylphenol (VIII). The Ritter reaction with NaCN in sulfuric acid-acetic acid yielded directly the cyclized imine (IX), generated from the intermediate nitrilium ion. Reduction to amine (X) was effected by catalytic hydrogenation in the presence of Raney Nickel, and this compound was finally oxidized to N-oxide the nitrone with H2O2 and a catalytic amount of sodium tungstate.