The use of environmental metrics to evaluate green chemistry improvements to the synthesis of (S,S)-reboxetine succinate

Abstract

The Pfizer Green Chemistry metrics program is described and exemplified with a case history involving the synthesis of (S,S)-reboxetine succinate. The initial route used a classical resolution approach and generated high levels of waste. This route was replaced by an enantiospecific synthesis which used Sharpless epoxidation chemistry, an enzymatic process to selectively protect a primary alcohol and a new efficient method of chiral morpholine construction as key steps. These improvements reduced the levels of waste produced by the synthesis by more than 90%. Detailed metrics starting from a common starting material (trans-cinnamyl alcohol) for all routes of synthesis are presented.