A three‐step radiosynthesis of 6‐[ 18 F]fluoro‐ L‐meta ‐tyrosine starting with [ 18 F]fluoride

The radiosynthesis of 6‐[ 18  F]fluoro‐L‐ m ‐tyrosine has generally been performed by electrophilic radiofluorination, which exhibits several drawbacks. In the present work, a three‐step radiochemical synthesis is described starting from [ 18  F]fluoride. The synthetic sequence, including isotopic exchange, Baeyer–Villiger oxidation, and hydrolysis, were examined comparing four fluorobenzophenone derivatives as labeling precursors. Of those, (2 S ,5 S )‐ tert ‐butyl 5‐(5‐acetyl‐2‐fluorobenzyl)‐2‐ tert ‐butyl‐3‐methyl‐4‐oxoimidazolidine‐1‐carboxylate (1a) and (2 S ,5 S )‐ tert ‐butyl 2‐ tert ‐butyl‐5‐(2‐fluoro‐5‐(2,2,2‐trifluoroacetyl)benzyl)‐3‐methyl‐4‐oxoimidazolidine‐1‐carboxylate (1d) proved to be the most suitable ones. 6‐[ 18  F]Fluoro‐L‐ m ‐tyrosine was obtained with overall radiochemical yields of 8–13% and an enantiomeric excess of up to 98%.