Optimization of the Industrial-Scale Manufacturing Process for Arformoterol through Classical Resolution of Formoterol

Brovana Inhalation Solution is a sterile, clear, colorless aqueous solution of the tartrate salt of arformoterol. Arformoterol, the R,R-enantiomer of formoterol, is a highly effective medication with improved pharmacodynamic properties, including increased receptor binding affinity and prolonged bronchodilation. This report describes the development of a robust, efficient, cost-effective, and commercially scalable process for the production of the targeted (R,R)-isomer of formoterol featuring a chiral resolution of inexpensive and readily available formoterol fumarate. This newly developed resolution process proved its efficacy by providing >99.90% chiral pure arformoterol with 74% overall yield.