Improved synthetic pathway for the derivatization of huprine scaffold

In the search of new huprine-like acetylcholinesterase binders, we have developed an improved, shorter, and high-scalable synthetic pathway for the huprine synthesis based on a Reformatsky reaction one-pot fragmentation/Friedlander condensation sequence. An extension for the one-pot synthesis of huprine-like 4-chloroquinolines is also presented. This modified route is particularly interesting as it allows to yield a huprine containing a functional group at position 9 in only three steps from commercially available material. (C) 2010 Elsevier Ltd. All rights reserved.