General methods for the preparation of α and/OR β deuterium labelled 6‐hydroxydopamine derivatives

A convenient synthetic method for the preparation of α and/or β deuterium-labelled 6-hydroxydopamines has been developed. Nitromethane was condensed with 2,4,5-trimethoxybenzaldehyde to give 2,4,5-trimethoxy-α-nitrostyrene (2). The nitroethylene side chain of 2 was reduced with sodium borodeuteride to afford β-[2H]-β-(2,4,5-trimethoxyphenyl)-α-nitroethane (3). A reduction with sodium borohydride in the presence of a deuterium source (e.g. EtOD) afforded mono and dideuterated α-[2H]-β- (2,4,5-trimethoxyphenyl)-α-nitroethanes (9, 10). A reduction of the nitrostyrene 2 with sodium borodeuteride in EtOD resulted in the isolation of α,β-[2H]-β-(2,4,5-trimethoxyphenyl)-α-nitroethanes (15 and 16). Subsequent reduction of the deuterated α-nitroethanes 3, 9, 10, 15 and 16 gave the appropriately labelled phenethylamine derivatives 5, 11, 12, 17 and 18. Removal of the phenol protecting groups afforded the deuterium labelled 2,4,5-trihydroxyphenethylamines (6-hydroxydopamines).