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[18F]fluorination/decarbonylation: new route to aryl [18F]fluorides
P K Chakraborty1, M R Kilbourn
1Department of Internal Medicine, University of Michigan, Ann Arbor 48109.
International Journal of Radiation Applications and Instrumentation. Part A, Applied Radiation and Isotopes
|January 1, 1991
Summary
A novel method synthesizes aryl [18F]fluorides using nucleophilic aromatic substitution and decarbonylation. This approach yields both no-carrier-added and carrier-added aryl [18F]fluorides efficiently within two hours.
Area of Science:
- Radiochemistry
- Organic Synthesis
- Medicinal Chemistry
Background:
- Aryl [18F]fluorides are crucial in positron emission tomography (PET) imaging.
- Existing methods for synthesizing aryl [18F]fluorides often require electron-withdrawing groups, limiting their scope.
- Development of versatile synthetic routes is essential for expanding the utility of [18F]labeled compounds.
Purpose of the Study:
- To develop a new synthetic route for aryl [18F]fluorides, particularly those lacking electron-withdrawing substituents.
- To establish a method for preparing both no-carrier-added (NCA) and carrier-added (CA) aryl [18F]fluorides.
- To optimize the synthesis for efficiency and reduced reaction times.
Main Methods:
- Nucleophilic aromatic substitution of fluoro or nitro groups using no-carrier-added [18F]fluoride to form [18F]fluorobenzaldehydes.
- Decarbonylation of the intermediate [18F]fluorobenzaldehydes using palladium on charcoal (Pd-C).
- Preparation of a key precursor, 4-fluoro-2-methoxy-5-methylbenzaldehyde, via methylation and formylation of 3-fluoro-4-methylphenol.
Main Results:
- Successful synthesis of NCA 3-[18F]fluorophenol (25-30% end-of-batch yield) from 2-methoxy-4-nitrobenzaldehyde.
- Successful synthesis of CA 3-[18F]fluoro-4-methylphenol (30-40% end-of-batch yield) from 4-fluoro-2-methoxy-5-methylbenzaldehyde.
- Overall synthesis time achieved in approximately 2 hours.
Conclusions:
- A new, efficient route to aryl [18F]fluorides, including those without electron-withdrawing groups, has been established.
- The method utilizes a removable activating group strategy for nucleophilic aromatic substitution with [18F]fluoride.
- This approach provides a valuable tool for the preparation of both NCA and CA aryl [18F]fluorides for potential radiopharmaceutical applications.