Synthesis of (R)-(–)-2-Fluoronorapomorphine — A Precursor for the Synthesis of (R)-(–)-2-Fluoro-N-[11C]propylnorapomorphine for Evaluation as a Dopamine D2 Agonist Ligand for PET Investigations

✍ Scribed by Kåre Søndergaard; Jesper Langgaard Kristensen; Nic Gillings; Mikael Begtrup

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 138 KB
• Volume: 2005
• Category: Article
• ISSN: 1434-193X
• DOI: 10.1002/ejoc.200500295

✦ Synopsis

Abstract

2‐Fluoronorapomorphine, the PET labelling precursor to 2‐fluoro‐N‐[^11^C]propylnorapomorphine, was prepared in 13 steps from codeine in a total yield of 10 %. Codeine was converted in four steps into N‐benzylnorcodeine which was oxidised by using the Swern protocol. Subsequent acid‐catalysed rearrangement afforded N‐benzylnormorphothebaine which was selectively triflylated at the 2‐position and pivaloylated at the 11‐position. The triflate underwent palladium‐catalysed amination with benzophenone imine. Amination conditions required sequential base addition to give substantial conversion of the triflate to the corresponding N‐substituted benzophenone imine. After acidic hydrolysis the resulting aniline was transformed into the 2‐fluoro compound via the Balz–Schiemann reaction. Hydrogenolysis of the N‐benzyl group followed by deprotection of the catechol moiety using BBr~3~ provided 2‐fluoronorapomorphine. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)