title: Synthesis of (18) F-Difluoromethylarenes from Aryl (Pseudo) Halides.
abstract: A general method for the synthesis of [(18) F]difluoromethylarenes from [(18) F]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 (18) F-fluorination precursors are readily prepared from aryl chlorides, bromides, iodides, and triflates. Seven (18) F-difluoromethylarene drug analogues and radiopharmaceuticals including Claritin, fluoxetine (Prozac), and [(18) F]DAA1106 were synthesized to show the potential of the method for applications in PET radiopharmaceutical design.
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA, 02138, USA.|Division of Nuclear Medicine and Molecular Imaging & Gordon Center for Medical Imaging, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA.
authors.forename: Hang
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA, 02138, USA.
authors.forename: Augustin
authors.initials: A
authors.lastname: Braun
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging & Gordon Center for Medical Imaging, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging & Gordon Center for Medical Imaging, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA. liang.steven@mgh.harvard.edu.|Department of Radiology, Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA. liang.steven@mgh.harvard.edu.
authors.forename: Steven H
authors.initials: SH
authors.lastname: Liang
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging & Gordon Center for Medical Imaging, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA. vasdev.neil@mgh.harvard.edu.|Department of Radiology, Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA. vasdev.neil@mgh.harvard.edu.
authors.forename: Neil
authors.initials: N
authors.lastname: Vasdev
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA, 02138, USA. ritter@chemistry.harvard.edu.|Division of Nuclear Medicine and Molecular Imaging & Gordon Center for Medical Imaging, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA. ritter@chemistry.harvard.edu.|Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, 45470, Mülheim an der Ruhr, Germany. ritter@chemistry.harvard.edu.
authors.forename: Tobias
authors.initials: T
authors.lastname: Ritter
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis / Q000737:chemistry; D005462:Fluorine Radioisotopes / Q000737:chemistry; D005473:Fluoxetine / Q000138:chemical synthesis / Q000737:chemistry; D054879:Halogenation; D007553:Isotope Labeling; D017336:Loratadine / Q000138:chemical synthesis / Q000737:chemistry; D010647:Phenyl Ethers / Q000138:chemical synthesis / Q000737:chemistry; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D000081:Acetamides; C118942:DAA 1106; D005462:Fluorine Radioisotopes; D010647:Phenyl Ethers; D019275:Radiopharmaceuticals; D005473:Fluoxetine; D017336:Loratadine; C000615276:Fluorine-18
keywords: aryl (pseudo) halides; difluoromethylarenes; fluorine-18; positron emission tomography; radiopharmaceuticals