Synthesis of 2-(Chlorodifluoromethyl)indoles for Nucleophilic Halogen Exchange with [F-18]Fluoride

The synthesis of 2-[F-18]trifluoromethylated indoles from the corresponding chlorodifluoromethyl precursors was found to proceed under milder conditions when compared to known metal-free nucleophilic exchange reactions with [F-18]fluoride on chlorodifluoro-methyl arenes. A key element in the reaction course is - most likely - a favorable elimination-addition mechanism on the 2-methyl position of the indole. Given the increasing interest in F-18-labelled compounds, this single step labeling methodology nicely complements the so far existing routes to 2-[F-18]trifluoromethylated indoles.