Triethylamine → (S)-N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-(2-hydroxyphenyl)benzoxazole-4-carboxamide Hydrochloride

Participants

Reaction Steps

A mixture of 2-(2-hydroxyphenyl)benzoxazole-4-carboxylic acid (50 mg, 0.2 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (75 mg, 0.4 mmol), 1-hydroxybenzotriazole (57 mg, 0.4 mmol) and (S)-(−)-3-aminoquinuclidine dihydrochloride (39 mg, 0.2 mmol) in DMF (5 mL) was stirred at room temperature for 10 min, then triethylamine (0.08 mL, 0.6 mmol) was added. The resulting reaction mixture was stirred at room temperature for 12 h. The reaction mixture was diluted with ethyl acetate (50 mL), and then treated with a saturated solution of sodium bicarbonate. The organic layer was isolated and the aqueous layer was further extracted with ethyl acetate (2×50 mL). The combined organics were washed with water (2×25 mL), brine (2×25 mL), dried (Na2SO4), filtered and concentrated. The crude material was purified by semi-preparative HPLC to afford the desired product (49 mg, 68%) as a light yellow solid: 1H NMR (500 MHz, CDCl3) δ 10.43 (s, 1H), 8.37 (d, J=6.7 Hz, 1H), 8.22 (dd, J=7.8, 1.0 Hz, 1H), 8.10 (dd, J=7.9, 1.6 Hz, 1H), 7.77 (dd, J=8.1, 0.9 Hz, 1H), 7.55-7.50 (m, 2H), 7.16 (dd, J=8.6, 0.6 Hz, 1H), 7.08 (t, J=7.0 Hz, 1H), 4.40-4.30 (m, 1H), 3.63-3.55 (m, 1H), 3.22-3.20 (m, 1H), 3.07-2.90 (m, 3H), 2.87-2.80 (m, 1H), 2.22-2.17 (m, 1H), 2.02-1.92 (m, 1H), 1.85-1.78 (m, 2H), 1.73-1.65 (m, 1H); MS (ESI+) m/z 364 (M+H).

Provenance & Evidence