Reaction Steps
To a solution of (R)-quinuclidin-3-amine dihydrochloride (120 mg, 0.603 mmol) and 1-(2-isocyanatopropan-2-yl)-3-(prop-1-en-2-yl)benzene (119 mg, 0.597 mmol) in THF (3 mL) was added triethylamine (168 uL, 1.21 mmol). The reaction mixture was stirred at room temperature for 18 h and then quenched with brine. The mixture was extracted with CHCl3 and the organic layer was dried (Na2SO4) and concentrated. The crude material was purified on a combiflash (SiO2 cartridge, CHCl3 and 2N NH3 in MeOH) to afford the corresponding urea (163 mg, 50%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.62 (t, J=1.6 Hz, 1H), 7.44 (dt, J=1.9, 7.0 Hz, 1H), 7.41-7.33 (m, 2H), 5.35 (br s, 1H), 5.11 (p, J=1.4 Hz, 1H), 4.84 (s, 1H), 4.21 (d, J=7.5 Hz, 1H), 3.70-3.61 (m, 1H), 3.13 (ddd, J=2.3, 9.3, 14.2 Hz, 1H), 2.71-2.54 (m, 3H), 2.30-2.22 (m, 1H), 2.15 (dd, J=0.8, 1.4, 3H), 2.05-1.96 (m, 1H), 1.65 (s, 3H), 1.64 (s, 3H), 1.65-1.60 (m, 1H) 1.54-1.45 (m, 2H), 1.22-1.12 (m, 1H), 0.95-0.80 (m, 1H) ppm. 13C NMR (400 MHz, CDCl3) δ 157.4, 148.5, 143.8, 141.3, 128.4, 124.4, 123.8, 122.2, 112.6, 55.2, 53.4, 46.2, 46.1, 44.5, 30.5, 30.4, 25.0, 22.2, 17.7, 8.9 ppm. Purity: 97.5% UPLCMS (210 nm); retention time 0.83 min; (M+1) 328.
