Unusual p‐Toluene Sulfonic Acid–Catalyzed Carbon–Carbon Bond Formation

Abstract

Attempts to synthesize the antidepressant drug atomoxetine directly by p-TSA‐catalyzed reaction between o‐cresol and N‐methyl‐3‐phenyl‐3‐hydroxypropyl amine in toluene at reflux temperature surprisingly resulted in the formation of ortho‐substituted phenol derivative. The structure is unambiguously confirmed by single crystal X-ray.

Keywords:

• Aromatic substitution
• atomoxetine
• antidepressant drug
• p‐toluenesulfonic acid
• carbon–carbon bond formation

Acknowledgment

We thank the management of Research and Development, Dr. Reddy's Laboratories Limited, Integrated Product Development, API, Unit‐III, for providing facilities to carry out this work. Co-operation extended by all the colleagues of Analytical R&D, Division of Discovery Research, is gratefully acknowledged.