Hydrochloric Acid → HCID 131733537, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of methyl 1-(4-((3-((S)-phenyl((((R)-quinuclidin-3-yloxy)carbonyl)amino)methyl)phenoxy)methyl)benzoyl)azetidine-3-carboxylate (I23, 350 mg, 0.60 mmol) in THF (3 mL) and MeOH (3 mL) was added an aqueous solution of LiOH (1 N, 1.2 mL, 1.2 mmol) at room temperature. The resulting mixture was stirred for 16 h before being cooled to 0° C. and acidified with 2 N HCl to pH 2. The resulting mixture was then concentrated in vacuo and azeotroped to dryness with toluene. To a solution of the carboxylic acid in DMF (5 mL) was then added (S)-3,5-dichloro-4-(2-(3,4-dimethoxyphenyl)-2-hydroxyethyl)pyridine 1-oxide (248 mg, 0.72 mmol) followed by 4-(dimethylamino)-pyridine (37 mg, 0.30 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (230 mg, 1.20 mmol). The resulting mixture was stirred at room temperature for 16 h and partitioned between EtOAc (50 mL) and water (20 mL). The organic layer was dried over MgSO4, filtered and the solvent was removed in vacuo. The residue was dissolved in DMSO (3.0 mL) and purified by preparative HPLC to provide the title compound (14 mg, 3% over two steps) as white solid.

Provenance & Evidence