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

Abstract

Abstract2‐Fluoronorapomorphine, the PET labelling precursor to 2‐fluoro‐N‐[11C]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 BBr3 provided 2‐fluoronorapomorphine. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Transition metals in organic synthesis: Highlights for the year 2005

“…Intermolecular carbon-nitrogen couplings were used in synthesis of (−)-2-fluoronorapomorphine [551], myrmicarin alkaloids [552] and trichostatin D [553]. A double N-arylation of 2,2 -biphenylene triflates with primary amines to give carbazoles was reported and this reaction was used in a synthesis of mukonine [213].…”

Biaryl Phosphane Ligands in Palladium‐Catalyzed Amination

“…[181] Interestingly a range of chelating phosphines proved unsuccessful in this system. It was also found that a large excess of base was necessary to effect a successful reaction and that the addition of a second batch of base to the reaction after 75 minutes was necessary in order to reach full conversion.…”

Direct amination of aryl halides with ammonia

“…23 However, the use of ammonia surrogates suffers either from low atom economy, the need for an additional cleavage step to liberate the primary aryl amine, the formation of waste, or high cost. 24 Therefore, ammonia is still by far the most interesting N-nucleophile. 5 In the following tutorial review, we will describe selected published efforts to achieve these research goals using metalbased complexes.…”