During the course of a recent drug discovery program, we required an efficient synthesis of 2-benzyloxy pyridine derivatives. The initial route relied on an alkylation of a 2-hydroxy pyridine intermediate, which proceeded in good overall yield but gave a mixture of products resulting from O- and N-alkylation. To avoid the need for separation of regioisomers, an alternative strategy was examined that involved nucleophilic addition to various 2-fluoropyridine derivatives. We found that additions of a variety of primary and secondary alcohols proceed in excellent yield under mild conditions (KOt-Bu, THF, 50 ˚C, 2-6 h) even when strongly electron donating groups are present on the 2-fluoropyridyl template. This approach would be well suited for rapid expansion of chemical space using parallel medicinal chemistry.
Heterocycles and Aromatics, Asymmetric Reactions and Syntheses and Total Synthesis of Complex Molecules
7:00 PM-9:00 PM, Wednesday, August 19, 2009 Walter E. Washington Convention Center -- Ballroom C, Poster