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

Abstract

The synthesis of 2-[18F]trifluoromethylated indoles from the corresponding chlorodifluoromethyl precursors was found to proceed under milder conditions when compared to known metal-free nucleophilic exchange reactions with [18F]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 18F-labelled compounds, this single step labeling methodology nicely complements the so far existing routes to 2-[18F]trifluoromethylated indoles.