Convergent, short synthesis of the muscarinic superagonist iperoxo

Up to now the availability of iperoxo, an important superagonist of the muscarinic acetylcholine receptors, was limited because the synthesis of its precursor, the iperoxo base, was characterized by low yields, laborious chromatography and low reproducibility. Here we report a robust convergent three-step synthesis by means of a Mannich reaction and nucleophilic substitution at the 3-nitro-Delta(2)-isoxazoline. The new route combines short reaction time, high reproducibility and an overall yield increased from 12% to 42%. (C) 2010 Elsevier Ltd. All rights reserved.