2-Amino-2′-[18F]fluorobenzhydrols, intermediates for the synthesis of [2′-18F]-1,4-benzodiazepine-2-ones

✍ Scribed by Peter Johnström; Sharon Stone-Elander

• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: French
• Weight: 609 KB
• Volume: 34
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/jlcr.2580340206

✦ Synopsis

Abstract

A method for synthesizing ^18^F‐labelled 2‐amino‐2′‐fluorobenzhydrols under nocarrier‐added conditions for use as radiolabelled intermediates in the synthesis of[2′‐^18^F]‐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‐[^18^F]Fluorobenzaldehyde, 5, synthesized in 55–70% yields by the nucleophilic aromatic substitution of 2‐nitrobenzaldehyde with the Kryptofix/K^+^ complex of [^18^F]F^−^, was subsequently reacted with the anilinodichloroborane coupling reagents with aromatic substitution occurring ortho to the amino group. The resulting 2‐amino‐2′‐[^18^F]fluorobenzhydrols, 7a ‐ 7d, were produced in conversions of 60–95% with reaction time ⩽ 10 min at room temperature or 60°C, depending on the aniline used. The total synthesis time, including evaporation of the target water, was 60–65 min. The total radiochemical conversions were of the order of 50–65% for 7a ‐ 7c and 35–45% for 7d, decay‐corrected and based on [^18^F]F^−^.