Synthesis of [methoxy‐³H]‐ and [methoxy‐¹¹C]‐ labelled raclopride. Specific dopamine‐D₂ receptor ligands

Radioactive labelled raclopride and its (R)‐isomer were prepared by O‐alkylation of the corresponding phenols with labelled methyl iodide. The syntheses of the two phenolic precursors from (R)‐ and (S)‐2‐aminomethyl‐1‐ethylpyrrolidine are described. Resolution of the racemic amine into the enantiomers was accomplished by fractional crystallization of the ditartrates. Coupling of the amines with 3,5‐dichloro‐2,6‐dimethoxybenzoyl chloride, followed by dealkylation, led to the diphenolic precursors. Mono‐alkylation of the corresponding precursor with [ 3 H]methyl iodide furnished the potent dopamine‐D 2 ligand [ 3 H]raclopride and its (R)‐isomer. [ 11 C]Methyl iodide was prepared from [ 11 C]carbon dioxide. Subsequent reaction with phenolic (S)‐precursor furnished [ 11 C]raclopride which has been used in positron emission tomography (PET) studies of the human brain.