A broadly applicable [18F]trifluoromethylation of aryl and heteroaryl iodides for PET imaging

Nat Chem. 2013 Nov;5(11):941-4. doi: 10.1038/nchem.1756. Epub 2013 Sep 8.

Abstract

Molecules labelled with the unnatural isotope fluorine-18 are used for positron emission tomography. Currently, this molecular imaging technology is not exploited at its full potential because many (18)F-labelled probes are inaccessible or notoriously difficult to produce. Typical challenges associated with (18)F radiochemistry are the short half-life of (18)F (<2 h), the use of sub-stoichiometric amounts of (18)F, relative to the precursor and other reagents, as well as the limited availability of parent (18)F sources of suitable reactivity ([(18)F]F(-) and [(18)F]F2). There is a high-priority demand for general methods allowing access to [(18)F]CF3-substituted molecules for application in pharmaceutical discovery programmes. We report the development of a process for the late-stage [(18)F]trifluoromethylation of (hetero)arenes from [(18)F]fluoride using commercially available reagents and (hetero)aryl iodides. This [(18)F]CuCF3-based protocol benefits from a large substrate scope and is characterized by its operational simplicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzene Derivatives / chemistry
  • Fluorine Radioisotopes / chemistry*
  • Fluoxetine / chemistry
  • Flutamide / chemistry
  • Hydrocarbons, Fluorinated / chemistry*
  • Iodobenzenes / chemistry*
  • Isotope Labeling / methods
  • Magnetic Resonance Spectroscopy
  • Methylation
  • Molecular Imaging
  • Molecular Structure
  • Positron-Emission Tomography / methods*

Substances

  • Benzene Derivatives
  • Fluorine Radioisotopes
  • Hydrocarbons, Fluorinated
  • Iodobenzenes
  • Fluoxetine
  • Flutamide

Associated data

  • PubChem-Substance/163826395
  • PubChem-Substance/163826396
  • PubChem-Substance/163826397
  • PubChem-Substance/163826398
  • PubChem-Substance/163826399
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  • PubChem-Substance/163826403
  • PubChem-Substance/163826404
  • PubChem-Substance/163826405
  • PubChem-Substance/163826406
  • PubChem-Substance/163826407
  • PubChem-Substance/163826408
  • PubChem-Substance/163826409
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  • PubChem-Substance/163826412
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