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

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.