Route optimization on selectivity and kilogram-scale synthesis of Vilanterol Trifenatate

Abstract

The development of an improved manufacturing process for the active ingredient vilanterol trifenatate, a potent drug for the treatment of chronic obstructive pulmonary disease (COPD), has been described with high yield and purity. The robust process was demonstrated on a multi kilogram scale. Wiped Film Molecular Distillation was applied to purify intermediates that were easily decomposed at high temperature, improving the yield by 10–15%. Meanwhile, the corresponding impurity was studied in detail and well resolved. Finally, vilanterol trifenatate was obtained pure in a very competitive total of 6 steps with a yield of 57.9%, and it was crystallized with greater than 99.9% purity, 99.9% chiral purity and no single major impurity >0.1%.