Acetic Acid → HCID 130473006, compound

Participants

Reaction Steps

To a solution of [(3R)-quinuclidin-3-yl]2-amino-2-phenylacetate bis hydrochloride salt (273 mg, 0.82 mmol) in ethanol (10 mL) was added the single enantiomer 2 of [2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3-ethoxy-4-methoxy-phenyl)ethyl] 5-formylthiophene-2-carboxylate (Intermediate 75, 135 mg, 0.27 mmol) and acetic acid (40 μL, 0.68 mmol). The resulting mixture was stirred at room temperature for 16 h. Sodium cyanoborohydride (45 mg, 0.68 mmol) was added and the reaction mixture was stirred at room temperature for a further 24 h. The solvent was removed by evaporation under reduced pressure and the residue was partitioned between 1 M aqueous hydrochloric acid (3 mL) and ethyl acetate (3 mL). The layers were separated and the aqueous phase was extracted with ethyl acetate (2×3 mL). The aqueous phase was basified with saturated aqueous sodium bicarbonate solution and then extracted with ethyl acetate (2×3 mL). The combined organic fractions were extracted with 1 M aqueous hydrochloric acid (2 mL). Brine (2 mL) was added and the aqueous layer was extracted with chloroform (5 mL and 2 mL). The combined organic fractions were washed with saturated aqueous sodium bicarbonate solution (2 mL), passed through a hydrophobic frit and the solvent was removed by evaporation under reduced pressure. Purification by preparative HPLC gave the title compound as an off-white solid (50 mg, 25%).

Provenance & Evidence