4-Fluorosulfonylpiperidines: Selective 5-HT2A ligands for the treatment of insomnia

α-Fluorosulfones, of general structure 3, were synthesized as an alternative approach to reduce the pKa of the piperidine ring in an existing series of sulfonyl piperidine 5-HT2A antagonists. This work led to the identification of 3b, a selective 5-HT2A antagonist that gave no significant increase in QTc in the anesthetized dog.