A Rapid and Efficient Method for the Fluoroalkylation of Amines and Amides. Development of a Method Suitable for Incorporation of the Short-Lived Positron Emitting Radionuclide Fluorine-18

Article abstract of DOI:10.1021/jo00380a030

We have described a two-step method for the preparation of fluoroalkyl-substituted amines and amides.The sequence involves fluoride ion displacement of a haloalkyl trifluoromethanesulfonate (triflate), followed by fluoroalkylation of the heteroatom system (amine or amide) by the fluoroalkyl halide.Alternatively, the fluoroalkyl halide can be prepared by halofluorination of a terminal olefin.These reactions have been used to prepare various fluoroalkyl derivatives of N-phenylpiperazine and N-fluoroalkyl derivatives of the neuroleptic agent spiperone (7).The sequence is rapid, convenient, and efficient, even when fluoride ion is the limiting reagent.Therefore, it is readily adaptable to the preparation of a variety of compounds labeled with the short half-life (t_1/2 = 110 min) positron-emitting radionuclide fluorine-18.