Reacción #2175493

Ecuación de reacción

2-Chloro-1-methyl pyridinium iodide

(S)-(−)-3-Aminoquinuclidine dihydrochloride

α,α,α-Trifluoro-p-toluic acid

Triethylamine

→

(S)—N-(quinuclidin-3-yl)-4-(trifluoromethyl)benzamide

Rendimiento 93.2%

Disolventes

water

Acetonitrile

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrowas subsequently injected into a Preparative HPLC instrument for purification
2. 2
   Concentraciónconcentrated under vacuum
3. 3
   Otrorecrystallized from 4 mL of Methanol/water (3:2)

Procedimiento

1.5 ml of Acetonitrile and Triethylamine (700 uL, 5.0 mmol) was added to a flask charged with (S)-(−)-3-Aminoquinuclidine dihydrochloride (199 mg, 1.0 mmol) and α,α,α-Trifluoro-p-toluic acid (209 mg, 1.1 mmol), followed by addition of 2-Chloro-1-methyl pyridinium iodide (383 mg, 1.5 mmol) at room temperature. After stirring overnight, about 2 ml of water 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, concentrated under vacuum, and then recrystallized from 4 mL of Methanol/water (3:2) to isolate white crystalline solid of (S)—N-(quinuclidin-3-yl)-4-(trifluoromethyl)benzamide (278 mg, 93% yield). 1H NMR (400 MHz, Methanol-D4) δ (ppm): 8.05 (d, J=8.2 Hz, 1H), 7.82 (d, J=8.2 Hz, 1H), 4.47 (m, 1H), 3.87 (t, J=11.8, 11.8 Hz, 1H), 3.38 (m, 4H), 2.39 (m, 1H), 2.27 (m, 2H), 2.13 (t, J=8.2 Hz, 1H). LCMS (ESI): m/z 299.1 (M+H [C15H17F3N2O]=299.13).

Fuente