Synthesis of no-carrier-added N-([¹⁸F]fluoroalkyl)spiperone derivatives

3-N-([¹⁸F]fluoroalkyl)spiperone derivatives (2, 3) can be prepared by N-alkylation of spiperone (1) with fluoroalkyl halides. The fluoroalkylating species 2-[¹⁸F]fluoroethyl bromide (7), 3-[¹⁸F]fluoropropyl bromide (8) and 4-[¹⁸F]fluorobutyl bromide (9) were prepared by [¹⁸F]fluoride ion displacement of the corresponding trifluoromethanesulfonates (triflates 4, 5, 6). By this method, the 2-[¹⁸F]fluoroethyl-, 3-[¹⁸F]fluoropropyl-, and 4-[¹⁸F]fluorobutyl spiperone derivatives (2a-c) can be prepared and purified rapidly and conveniently, within 40 min, in yields of 30-40% (end of synthesis, EOS). An alternative approach, suitable for the preparation of 2-[¹⁸F]fluoroalkyl (ethyl, propyl, butyl, pentyl and hexyl) spiperone derivatives (3a-d), involves iodo[¹⁸F]fluorination of terminal olefins, followed by N-alkylation of spiperone. This sequence is less convenient and proceeds in lower overall yields (<5%).