A new modified "Montanari oxidation process" by means of chlorine dissolved in the reaction solvent as oxidant and TEMPO as catalyst:: Oxidation of 3-S-quinuclidinol to 3-quinuclidinone

Results from a process improvement project for preparation of 3-R-quinuclidinol, a highly valuable intermediate for several muscarine-active compounds are described. The studied process was based on the kinetic resolution of racemic 3-quinuclidinol and thus involved a large side-stream production. Our outline for process improvement is based on that this side stream can be recycled by a two-step sequence of oxidation and reduction processes. Findings concerning the conversion of 3-S-quinuclidinol into 3-quinuclidinone by using an improved oxidation process based on TEMPO (2,2,6,6-tetramethylpiperidin-1-oxyl radical) and molecular chlorine are discussed in detail. The developed oxidation procedure affords nearly quantitatively yield in the conversion of 3-S-quinuclidinol into 3-quinuclidinone.