Aniline → ethyl 2-[3-[(N-[(3R)-quinuclidin-3-yl]oxycarbonyl-anilino)methyl]phenyl]acetate

Participants

Reaction Conditions

Reaction Steps

A mixture of ethyl 2-[3-(bromomethyl)phenyl]acetate (600 mg, 2.33 mmol), aniline (202 mg, 2.21 mmol) and potassium carbonate (420 mg, 3.04 mmol) in 1V, N-dimethylformamide (15 mL) was heated to 90° C. for 18 hours. After cooling to room temperature, the reaction was filtered and the solvent was removed in vacuo. The residue was taken up in ethyl acetate and washed with brine (3×20 mL). The organic phase was passed through a hydrophobic fit and the solvent was removed in vacuo. The crude material was dissolved in acetonitrile (5 mL), and (R)-quinuclidin-3-yl carbonochloridate hydrochloride (530 mg, 2.35 mmol) was added. The resulting mixture was heated to 100° C. for 30 minutes under microwave irradiation. The solvent was removed in vacuo, then the residue was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution. The organic layer was washed with brine, passed through a hydrophobic fit and the solvent was removed in vacuo. The residue was purified by silica gel column chromatography eluting sequentially with ethyl acetate, 10% methanol in ethyl acetate and 10% 7N methanolic ammonia in ethyl acetate to afford the title compound as a yellow solid (331 mg, 35%).

Provenance & Evidence