Process to Prepare Vilanterol Trifenatate

Abstract

In one aspect, a process for the preparation of vilanterol ((R)-4-(2-((6-(2-((2,6-dichlorobenzyl)oxy)ethoxy)hexyl)amino)-1-hydroxyethyl)-2-(hydroxymethyl)phenol; Compound VI) or a pharmaceutically acceptable salt thereof, comprises the following steps wherein steps A to B(i) are carried out as a one-pot or telescoped process: A) coupling the compound (5R)-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-1,3-oxazolidin-2-one (Compound II) with 2-[2-(6-bromohexyloxy)-ethoxymethyl]-1,3-dichlorobenzene (Compound III) in the presence of a base, in an organic solvent; and B) (i) adding a base to the reaction mixture formed in step A to remove the oxazolidinone protecting group, to form Compound V; (ii) converting Compound V to vilanterol (compound VI) or a pharmaceutically acceptable salt thereof. In another aspect, a process for the preparation of vilanterol ((R)-4-(2-((6-(2-((2,6-dichlorobenzyl)oxy)ethoxy)hexyl)amino)-1-hydroxyethyl)-2-(hydroxymethyl)phenol; Compound VI) or a pharmaceutically acceptable salt thereof, comprises coupling the compound (5R)-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-1,3-oxazolidin-2-one (Compound II) with 2-[2-(6-bromohexyloxy)-ethoxymethyl]-1,3-dichlorobenzene (Compound III) and converting the product formed to vilanterol or a pharmaceutically acceptable salt thereof, wherein during the process either no, or only one, intermediate compound is isolated.

Dependencies are inferred from the claim text.