Synthesis of 18F‐Difluoromethylarenes from Aryl (Pseudo) Halides

• DOI: 10.1002/ange.201604106
• Publication Date: 2016-08-05T08:13:48Z
• Authors: Hang Shi; Augustin Braun; Lu Wang; Steven H. Liang; Neil Vasdev; Tobias Ritter
• Keywords: Fluorine Radioisotopes; Halogenation; Phenyl Ethers; Loratadine; 01 natural sciences; 0104 chemical sciences; Fluoxetine; Isotope Labeling; Positron-Emission Tomography; Acetamides; Radiopharmaceuticals

AbstractA general method for the synthesis of [18F]difluoromethylarenes from [18F]fluoride for radiopharmaceutical discovery is reported. The method is practical, operationally simple, tolerates a wide scope of functional groups, and enables the labeling of a variety of arenes and heteroarenes with radiochemical yields (RCYs, not decay‐corrected) from 10 to 60 %. The 18F‐fluorination precursors are readily prepared from aryl chlorides, bromides, iodides, and triflates. Seven 18F‐difluoromethylarene drug analogues and radiopharmaceuticals including Claritin, fluoxetine (Prozac), and [18F]DAA1106 were synthesized to show the potential of the method for applications in PET radiopharmaceutical design.