¹⁸F-Labeled building blocks from the type of [¹⁸F]fluorophenylazocarboxylic-tert-butyl esters offer a rapid, mild, and reliable method for the ¹⁸F-fluoroarylation of biomolecules. Two series of azocarboxamides were synthesized as potential radioligands for dopamine D3 and the μ-opioid receptor, revealing compounds 3d and 3e with single-digit and sub-nanomolar affinity for the D3 receptor and compound 4c with only micromolar affinity for the μ-opioid receptor, but enhanced selectivity for the μ-subtype in comparison to the lead compound AH-7921. A "minimalist procedure" without the use of a cryptand and base for the preparation of 4-[¹⁸F]fluorophenylazocarboxylic-tert-butyl ester [¹⁸F]2a was established, together with the radiosynthesis of methyl-, methoxy-, and phenyl-substituted derivatives ([¹⁸F]2b-f). With the substituted [¹⁸F]fluorophenylazocarbylates in hand, two prototype azocarboxylates radioligands were synthesized by ¹⁸F-fluoroarylation, namely the methoxy azocarboxamide [¹⁸F]3d as the D3 receptor radioligand and [¹⁸F]4a as a prototype structure of the μ-opioid receptor radioligand. By introducing the new series of [¹⁸F]fluorophenylazocarboxylic-tert-butyl esters, the method of ¹⁸F-fluoroarylation was significantly expanded, thereby demonstrating the versatility of ¹⁸F-labeled phenylazocarboxylates for the design of potential radiotracers for positron emission tomography .

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