Stereoretentive Etherification of an alpha-Aryl-beta-amino Alcohol Using a Selective Aziridinium Ring Opening for the Synthesis of AZD7594

摘要

A selective aziridinium ring-opening was used to etherify an alpha-aryl-beta-amino alcohol with stereochemical retention. This transformation was achieved in a biphasic system to address phenoxide solubility and the formation of a sulfonate ester impurity. The protecting group strategy was directed by a stability study of the activated alpha-aryl-beta-amino alcohol in this system. Process analytical techniques were used to establish reaction understanding, and mixing on large scale was modeled in silico. The process provided a selective and efficient method of preparing the nonsteroidal, inhaled selective glucocorticoid receptor modulator AZD7594.