Acetic Acid → 2-(4-((((R)-2-Hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl)amino)methyl)-2-methylphenoxy)ethyl 4-((3-((S)-phenyl((((R)-quinuclidin-3-yloxy)carbonyl)amino)methyl) phenoxy)methyl)benzoate

Participants

Reaction Steps

To a suspension of (R)-5-(2-amino-1-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one hydrochloride (0.211 g, 0.83 mmol) in methanol (6 mL) was added triethylamine (0.229 mL, 1.65 mmol). The mixture was stirred for 10 minutes and then a solution of 2-(4-formyl-2-methylphenoxy)ethyl 4-((3-((S)-phenyl((((R)-quinuclidin-3-yloxy)carbonyl)amino)methyl)phenoxy)methyl)benzoate (0.445 g, 0.69 mmol) in methanol (2 mL) was added. The mixture was stirred at RT for 1 hour. Sodium triacetoxyborohydride (0.292 g, 1.38 mmol) followed by acetic acid (0.188 mL, 3.28 mmol) added and the reaction continued for a further 18 hours. The reaction mixture was quenched with water and evaporated at reduced pressure. The residue dissolved in iso-butanol and washed with water. The organic phase was evaporated at reduced pressure and the crude material was purified by reverse phase preparative HPLC to afford the title compound (0.065 g, 11%).

Provenance & Evidence