N ‐(Benzyloxy)‐ N ‐(pivaloyloxy)‐4‐(trifluoromethyl)‐benzamide

Abstract

This chapter presents the procedure for the N‐(Benzyloxy)‐N‐(pivaloyloxy)‐4‐(trifluoromethyl)‐benzamide which belongs to the N‐(alkoxy)‐N‐(acyloxy)benzamide class of anomeric amides. In this class of compounds, in order to satisfy the electron demand of the two oxygen substituents, the resonance of the nitrogen lone pair with the amide carbonyl is largely diminished. This results in an sp 3 configuration and pyramidalization at nitrogen. The authors have used N‐(Benzyloxy)‐N‐(pivaloyloxy)‐4‐(trifluoromethyl)‐benzamide to selectively edit secondary amines containing a range of functional groups and heterocycles. Nitrogen deletion of cyclic secondary amines results in a ring contraction, which has been applied to give substituted cyclobutene products from pyrrolidine precursors. This methodology also enabled a new synthetic route to the chemotherapeutic Pemetrexed and enabled the late‐stage editing of the kinase inhibitor Lapatinib.