Generation of 1-azabicyclo[3.2.1]octane and 5-azatricyclo[3.2.1.0(2,7)] octane systems by carbenium ion rearrangements during production of the antihistamine drug Quifenadine

摘要

Dehydration of ethyl 3-hydroxyquinuclidine-3-carboxylate is one of the key steps during production of the antihistamine drug Quifenadine (Phencarol). The side products of this process were isolated and their structures proved using NMR spectroscopy. Carbenium ion rearrangements of quinuclidine-3-carboxylate gave rise to 1-azabicyclo[3.2.1 ]octane and 5-azatricyclo[3.2.1.0(2,7)]octane systems, which serve as impurity standards for the manufacturing process of Quifenadine and are also interesting building blocks for medicinal chemistry. (C) 2019 Elsevier Ltd. All rights reserved.