22151-78-6Relevant articles and documents
Improved synthesis of buprenorphine from thebaine and/or oripavine via palladium-catalyzed N-demethylation/acylation and/or concomitant O-demethylation
MacHara, Ales,Werner, Lukas,Endoma-Arias, Mary Ann,Cox, D. Phillip,Hudlicky, Tomas
experimental part, p. 613 - 626 (2012/05/20)
An improved preparation of buprenorphine via palladium-catalyzed N-demethylation/acylation is reported. Three routes were investigated and compared in overall yield. The first involved N-demethylation/acylation of an advanced intermediate obtained from thebaine followed by hydrolysis of the N-acetamide and alkylation with cyclopropylmethyl bromide and/or reduction of the N-acetyl group with the Schwartz reagent followed by N-alkylation. The second route employed cyclopropylcarboxylic acid anhydride in the N-demethylation/acylation protocol and subsequent reduction of the cyclopropylcarboxamide by either lithium aluminum hydride or under hydrosilylation conditions. Both of these routes originated in thebaine and therefore required O-demethylation as a final step. The third route employed an N-demethylation/acylation sequence starting from oripavine rather than thebaine, thus avoiding the O-demethylation. The routes are compared for overall efficiency and experimental and spectral data are provided for all new compounds. Copyright
