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

As an example of applying the electrochemical method in radiofluorination a new procedure was developed for preparing [F-18]fluorophenylalanine by direct use of [18F]fluoride. Several protecting groups for amino and carboxylic function of phenlylalanine 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 center dot 3HF as supporting electrolyte and temperatures between 0 and -10 degrees C. By variation of working potential (1.5-2.0V) and chloride concentration (added as supporting electrolyte, 0.0-0.36M) 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 (c) 2005 John Wiley & Sons, Ltd.