Synthesis and Absolute Configuration Assignment of 9-Hydroxyrisperidone Enantiomers

The enantiomers of 9-hydroxyrisperidone, the major metabolite of risperidone and the active component of the antipsychotic drug Invega®, were synthesized by efficient methods. Their optical rotation and enantiomeric purity were characterized for the first time. The absolute configurations were assigned by comparing 1H NMR chemical shifts of Mosher esters of a key stereoisomeric intermediate. Thus, the stereoisomeric center of (+)-9-hydroxyrisperidone has been assigned as the S configuration, and its enantiomer has the configuration R.