TY - JOUR
T1 - 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
AU - Søndergaard, Kåre
AU - Kristensen, Jesper Langgaard
AU - Gillings, Nic
AU - Begtrup, M.
PY - 2005/10/14
Y1 - 2005/10/14
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=27144453646&partnerID=8YFLogxK
U2 - 10.1002/ejoc.200500295
DO - 10.1002/ejoc.200500295
M3 - Journal article
AN - SCOPUS:27144453646
SN - 1434-193X
SP - 4428
EP - 4433
JO - European Journal of Organic Chemistry
JF - European Journal of Organic Chemistry
IS - 20
ER -