Regioselective syntheses of deuterium labelled 6‐hydroxydopamines

Convenient syntheses of 2,4‐,α,α‐ and β,β‐deuterium labelled 6‐hydroxydopamines have been developed. 2,4,5‐Trimethoxybenzaldehyde ( 1 ) was reductively aminated to give 2,4,5‐trimethoxybenzylamine ( 2 ). Quaternization of the amine with methyliodide followed by displacement with cyanide gave 2,4,5‐trimethoxybenzylcyanide ( 4 ). A LiAID 4 reduction of 4 gave α,α‐[ 2 H]‐β‐(2,4,5‐trimethoxyphenyl)‐ethylamine ( 5 ). Treatment of benzylcyanide 4 with n‐butyllithium/D 2 O gave α,α‐[ 2 H]‐α‐cyano‐2,4,5‐trimethoxytoluene ( 7 ) which upon reduction afforded β,β‐[ 2 H]‐β‐(2,4,5‐trimethoxyphenyl)‐ethylamine ( 8 ). Treatment of 2,4,5‐trimethoxydimethylbenzylamine 2 with n‐butyllithium/D 2 O gave 3,6‐[ 2 H]‐2,4,5‐trimethoxydimethyl‐benzylamine ( 10 ). The ring deuterium atoms were retained through subsequent steps to afford β‐(3,6‐[ 2 H]‐2,4,5‐trimethoxyphenyl)‐ethylamine ( 13 ). Removal of the phenol protecting groups afforded the deuterium labelled 2,4,5‐trihydroxyphenethylamines (6‐hydroxydopamines).