Thionyl Chloride → N-(1-azabicyclo[2.2.2]oct-3-yl)-2-(4-chlorophenyl)benzoxazole-4-carboxamide

Participants

Reaction Steps

A 25 mL round bottomed flask equipped with a reflux condenser was purged with nitrogen and charged with 2-(4-chlorophenyl)benzoxazole-4-carboxylic acid (0.050 g, 0.18 mmol) followed by thionyl chloride (5 mL). The resulting suspension was heated to reflux for 1 hr, after which time a light yellow solution was obtained. The reaction was then cooled and the thionyl chloride removed under reduced pressure affording an off-white solid. This solid was dissolved in methylene chloride (10 mL) and quinuclidine dihydrochloride (0.056 g, 0.27 mmol) added followed by the drop-wise addition of diisopropylethylamine (0.371 g, 2.87 mmol) over 5 min. After stirring at room temperature for 3 hrs the reaction was quenched by the addition of water (10 mL) and the organic layer separated. Subsequent washing of the organic layer with water (10 mL) followed by brine (10 mL), drying over MgSO4, filtration and concentration afforded a tan solid. This solid was purified by preparative HPLC to afford 0.012 g (17% yield) of N-(1-azabicyclo[2.2.2]oct-3-yl)-2-(4-chlorophenyl)benzoxazole-4-carboxamide as an white solid: mp 194-196° C.; 1H NMR (500 MHz, DMSO-d6) δ 9.13 (m, 1H), 8.23 (dd, J=6.7, 1.9 Hz, 2H), 8.03 (dd, J=8.2, 0.9 Hz, 1H), 7.97 (dd, J=7.7, 0.9 Hz, 1H), 7.78 (dd, J=6.7, 1.9 Hz, 2H), 7.58 (t, J=8.0 Hz, 1H), 4.09 (m, 1H), 3.28 (m, 1H), 2.85 (m, 2H), 2.75 (m, 2H), 2.63 (m, 1H), 2.08 (m, 1H), 1.99 (m, 1H), 1.65 (m, 2H), 1.57 (m, 1H); MS (ESI) m/z 382 [M+H]+.

Provenance & Evidence