2-AMINO-2'-[F-18]FLUOROBENZHYDROLS, INTERMEDIATES FOR THE SYNTHESIS OF [2'-F-18]-1,4-BENZODIAZEPINE-2-ONES

A method for synthesizing F-18-labelled 2-amino-2'-fluorobenzhydrols u nder no-carrier-added conditions for use as radiolabelled intermediate s in the synthesis of [2'-F-18]-1,4-benzodiazepine-2-ones is presented . Anilinodichloroborane reagents were formed by the reaction of boron trichloride with 4-chloro-N-methylaniline, 6a, 4-nitro-N-methylaniline , 6b, 4-nitro-N-ethylaniline, 6c, and 4-chloro-N-(2,2,2-trifluoroethyl )aniline, 6d. 2-[F-18]Fluorobenzaldehyde, 5, synthesized in 55-70% yie lds by the nucleophilic aromatic substitution of 2-nitrobenzaldehyde w ith the Kryptofix/K+ complex of [F-18]F-, was subsequently reacted wit h the anilinodichloroborane coupling reagents with aromatic substituti on occurring ortho to the amino group. The resulting 2-amino-2'-[F-18] fluorobenzhydrols, 7a - 7d, were produced in conversions of 60-95% wit h reaction time less than or equal to 10 min at room temperature or 60 degrees C, depending on the aniline used. The total synthesis time, i ncluding evaporation of the target water, was 60-65 min. The total rad iochemical conversions were of the order of 50-65% for 7a - 7c and 35- 45% for 7d, decay-corrected and based on [F-18]F-.