Electrochemical radiofluorination. 3. Direct labeling of phenylalanine derivatives with [18F]fluoride after anodic oxidation

Abstract

As an example of applying the electrochemical method in radiofluorination a new procedure was developed for preparing [18F]fluorophenylalanine by direct use of [18F]fluoride. Several protecting groups for amino and carboxylic function of phenylalanine were investigated. Best results were obtained for N-trifluoroacetylphenylalanine methyl ester (1) (10.5±2.5%) with a relative isomeric distribution of 50.5±1.5% ortho isomer, 11.5±1.5% meta isomer and 38.8±2.1% para isomer. Optimized reaction conditions were with Et3N·3HF as supporting electrolyte and temperatures between 0 and –10°C. By variation of working potential (1.5–2.0 V) and chloride concentration (added as supporting electrolyte, 0.0–0.36 M) it was demonstrated that an indirect electrolysis as reaction mechanism or a halogen exchange (halex) reaction with primary formation of a chlorinated product followed by halogen exchange are highly improbable. Copyright © 2005 John Wiley & Sons, Ltd.