Triethylamine → (S)-N-(quinuclidin-3-yl)-4-(thiophen-2-yl)benzamide

Participants

Reaction Steps

0.5 ml of Acetonitrile, 0.25 ml of water, and Triethylamine (108 uL, 0.78 mmol) was dissolved in a flask charged with (S)-(−)-3-Aminoquinuclidine dihydrochloride (47.8 mg, 0.2 mmol) at room temperature. To the mixture was added 4-(2-Thienyl)benzoic acid (49 mg, 2.4 mmol) and 1-hydroxy benzotriazole (33.8 mg, 0.25 mmol) followed by addition of N,N′-Diisopropyl carbodimide (38.7 uL, 0.25 mmol). The mixture was then stirred overnight at room temperature. About 2 ml of methanol was added to reaction mixture to resolve a clear solution that was subsequently injected into a Preparative HPLC instrument for purification. Desired fractions were combined and concentrated under vacuum. (S)—N-(quinuclidin-3-yl) -4-(thiophen-2-yl)benzamide (8.2 mg, 13% yield) was isolated at an oil. 1H NMR (400 MHz, Methanol-D4) δ (ppm): 7.90 (dt, J=8.7, 1.9 Hz, 2H), 7.76 (dt, J=8.6, 1.9 Hz, 2H), 7.53 (dd, J=3.7, 1.1 Hz, 1H), 7.48 (dd, J=4.0, 1.1 Hz, 1H), 7.14 (dd, J=3.5, 1.6 Hz, 1H), 4.45 (m, 1H), 3.86 (ddd, J=10.0, 3.0, 2.5 Hz, 1H), 3.37 (m, 4H), 2.38 (m, 1H), 2.26 (m, 1H), 2.11 (m, 2H), 1.95 (m, 1H). LCMS (ESI): m/z 313.1 (M+H [C18H20N2OS]=313.13).

Provenance & Evidence