Acetic Acid → HCID 118142792, compound

Participants

Reaction Steps

A suspension of (R)-quinuclidin-3-yl 2-amino-2-(3-fluorophenyl)acetate bis hydrochloride salt (0.176 g, 0.500 mmol) in EtOAc (5 mL) was added with Et3N (0.150 mL, 1.10 mmol). The reaction mixture was stirred at room temperature for 2 h. The precipitate obtained was filtered, washed with EtOAc (˜5 mL) and the solvent was removed in vacuo. This residue was dissolved in CH3CN (5 mL) and to the solution was added [(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl]5-formylthiophene-2-carboxylate (0.220 g, 0.456 mmol) followed by acetic acid (0.026 mL, 0.456 mmol). The reaction mixture was stirred at room temperature for 20 h. NaBH(OAc)3 (0.265 g, 1.25 mmol) was added and the reaction mixture was stirred at room temperature for a further 24 h. The excess solvent was removed in vacuo and the residue was partitioned between EtOAc (30 mL) and saturated aqueous NaHCO3 solution (20 mL). The organic layer was washed with saturated brine (2×15 mL), separated and filtered through a phase separator cartridge and the solvent was removed in vacuo. Purification by preparative HPLC gave the title compound (1:1 mixture of diastereoisomers) as a pale yellow solid (200 mg, 59%).

Provenance & Evidence