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Synthesis of (R)-(-)-2-fluoronorapomorphine - A precursor for the synthesis of (R)-(-)-2-fluoro-N-[C]propylnorapomorphine for evaluation as a dopamine D agonist ligand for PET investigations

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2-Fluoronorapomorphine, the PET labelling precursor to 2-fluoro-N-[ 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. Subseguent 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 provided 2-fluoronorapomorphine.
OriginalsprogEngelsk
TidsskriftEuropean Journal of Organic Chemistry
Udgave nummer20
Sider (fra-til)4428-4433
Antal sider6
ISSN1434-193X
DOI
StatusUdgivet - 14 okt. 2005

ID: 45438091