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Synthesis of ( R )‐(–)‐2‐Fluoronorapomorphine — A Precursor for the Synthesis of ( R )‐(–)‐2‐Fluoro‐ N ‐[ 11 C]propylnorapomorphine for Evaluation as a Dopamine D 2 Agonist Ligand for PET Investigations
Author(s) -
Søndergaard Kåre,
Langgaard Kristensen Jesper,
Gillings Nic,
Begtrup Mikael
Publication year - 2005
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200500295
Subject(s) - chemistry , amination , imine , benzophenone , trifluoromethanesulfonate , hydrogenolysis , moiety , swern oxidation , reductive amination , aniline , medicinal chemistry , palladium , stereochemistry , organic chemistry , catalysis , dimethyl sulfoxide
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)