FeCl3-catalyzed oxidative decarboxylation of aryl/heteroaryl acetic acids: preparation of selected API impurities

Abstract

There is an ever-increasing demand for impurity compounds for use in impurity profiling as regulatory agencies seek information during registration. Herein, we report the FeCl₃-catalyzed oxidative decarboxylation of aryl- and heteroaryl acetic acids to the corresponding carbonyl compounds. A variety of useful aldehydes and ketones were prepared in a simple one-pot transformation by employing an environmentally benign, low-cost, and readily available iron salt. The utility of this method has been demonstrated by preparing five valuable API impurities including a multi-gram-scale synthesis of ketorolac impurity B for the first time.