A practical asymmetric synthesis of (R)-fluoxetine and its major metabolite (R)-norfluoxetine

A convenient and chromatography-free synthesis for the enantiomers of fluoxetine and norfluoxetine is described. The synthesis relied on the use of the CBS reduction, and Hofman rearrangement to establish the key common intermediate 5, and enrichment of optical purity of the final product by crystallization as the tartrate salt.