The synthesis of (R)- and (S)-[N-methyl-11C]β, β-difluoromethamphetamine for the investigation of the binding mechanism of biogenic amines in vivo

In an attempt to elucidate the contribution of the extent of nitrogen protonation on the in vivo binding of methamphetamine in the brain, the enantiomers of [N-methyl-11C]β,β-difluoroamphetamine (4) were prepared for use in positron emission tomography (PET) studies. Thus, the enantiomers of β,β-difluoroamphetamine were prepared from trans-β-methylstyrene, via bromination, conversion into the azirine, fluorination and resolution as the tartrate salts. (R)- and (S)-β,β-difluoroamphetamine (3) were then each labelled with carbon-11 (t1/2=20.4 min) by N-methylation of the corresponding homochiral β,β-difluoroamphetamine with [11C]methyl iodide. The labelled products were each synthesised, purified and formulated in 35 min, starting from [11C]carbon dioxide in 15–16% decay-corrected radiochemical yield, with a radiochemical purity of >99% and specific radioactivity of 50–150 GBq μmol−1 at end of synthesis.