In a related procedure, 2-fluoro-3-hydroxypyridine (IX) was treated with dimethylamine to provide (dimethylamino)pyridine (X). This was coupled to alcohol (III) to give ether (XI). Alternatively, (XI) was prepared by coupling fluoropyridine (IX) with alcohol (III) and subsequently treated with dimethylamine. Quaternization by means of methyl trifluoromethanesulfonate produced trimethylammonium derivative (XIII). Further displacement in (XIII) using [18F]KF-Kryptofix K222 complex provided radiolabeled fluoropyridine (VI), which was finally deprotected as above.

Title radiolabeled compound has been obtained by several related procedures. Protection of (S)-2-azetidinecarboxylic acid (I) with tert-butyl dicarbonate provided carbamate (II), which was reduced to alcohol (III) using borane-dimethyl sulfide in THF at -78 C (1, 3). Subsequent coupling of (III) with 3-hydroxy-2-nitropyridine (IV) under Mitsunobu conditions gave ether (V). Introduction of the 18F in (IV) was performed by means of [18F]KF-Kryptofix K222 complex in DMSO, either by conventional heating at 150 C or by microwave activation yielding (VI). The resulting radiolabeled fluoropyridine (VI) was finally deprotected with trifluoroacetic acid in CH2Cl2.

In an alternative procedure, Mitsunobu coupling of alcohol (III) with 3-hydroxy-2-iodopyridine (VII) provided ether (VIII). The iodo atom of (III) was then displaced using [18F]KF-Kryptofix K222 complex in DMSO to provide radiolabeled precursor (VI), which was finally deprotected with trifluoroacetic acid.