Water → methyl 4-((3-((S)-phenyl((((R)-quinuclidin-3-yloxy)carbonyl)amino)methyl)phenoxy)methyl)benzoate

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of (S)-methyl 4-((3-(amino(phenyl)methyl)phenoxy)methyl)-benzoate hydrochloride (I13, 12.0 g, 31.3 mmol) in pyridine (100 mL) at 0° C. was added portion-wise (R)-quinuclidin-3-yl carbonochloridate (8.50 g, 37.5 mmol, prepared as previously reported for Int 6, Step 6). The reaction was stirred at 0° C. for 1 hour and then allowed to warm to RT for 16 h. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate (×3). The combined extracts were washed with brine, dried over sodium sulfate, filtered and the solvent was removed in vacuo. The crude material was purified by chromatography on a KP-NH Biotage cartridge eluting with 0-20% methanol in ethyl acetate to afford the title compound (10.3 g, 66%).

Provenance & Evidence