4-[3-(Chloromethyl)-1,2,4-oxadiazol-5-yl]pyridine → (R)-3-((R)-2-phenyl-2-(phenylamino)acetoxy)-1-((5-(pyridin-4-yl)-1,2,4-oxadiazol-3-yl)methyl)-1-azoniabicyclo[2.2.2]octane chloride

Participants

Reaction Conditions

Reaction Steps

3-(Chloromethyl)-5-(pyridin-4-yl)-1,2,4-oxadiazole (I51) (45.0 mg, 0.23 mmol) was added to a solution of (R)—((R)-quinuclidin-3-yl) 2-phenyl-2-(phenylamino)acetate (diastereomer 1 of I2) (50 mg, 0.15 mmol) in EtOAc (2 ml). The reaction mixture was heated under microwave irradiation at 80° C. for 3 hours. The solvent was evaporated, and the residue was triturated with Et2O, filtered and dried. The product was purified by flash-chromatography (DCM/MeOH=97/3 to 9/1) and then by preparative HPLC (eluents: CH3CN/H2O) to obtain (R)-3-((R)-2-phenyl-2-(phenylamino)acetoxy)-1-((5-(pyridin-4-yl)-1,2,4-oxadiazol-3-yl)methyl)-1-azoniabicyclo[2.2.2]octane chloride (32.3 mg, 29.0% yield).

Provenance & Evidence