Reaction Steps
7-amino-4-methyl-5-(3-isopropoxyphenyl)-2-(3-phenylpropyl)-2-aza-bicyclo[3.3.1 ]nonane (2.7) (3.07 g, 7.8 mmole) was dissolved in glacial acetic acid (20 mL), 48% HBr (32.5 ml) was added, and the solution was heated to reflux for 15 h. The reaction mixture was allowed to cool to room temperature, poured into ice (100 g), and the pH was raised to 10 with 50% NaOH. The aqueous layer was extracted with 3:1 CH2Cl2:THF (3×100 mL). The combined organic extracts were dried (Na2SO4), filtered, and concentrated in vacuu. The crude product was purified by flash chromatography using silica gel and eluted with 65:35 CH2Cl2:CMA-80 to yield 2.8 g (88.3%) of the desired product as an off-white solid. The analytical sample was prepared by dissolving the free base in CHCl3, acidifying with HCl in ether, and precipitated with ether. The ether/CHCl3 mixture was decanted and the percipitate taken up in MeOH. The product was then precipitated out of the MeOH with ether. The solvent was decanted and the resultant material was dried under vacuum at 50° C. overnight. [α]D20=−20.5 (c 1.03, MeOH). 1H NMR (CDC13) δ 7.27-7.07 (m, 6H), 6.65-6.58 (m, 3H), 4.33 (br, 2H), 3.54 (br, 1H), 2.79 (m, 1H), 2.66-2.53 (m, 3H), 2.46 (t, J=7.0 Hz, 2H,), 2.31 (m, 3H), 2.04 (br, 1H), 1.77 (t, J=7.2, 2H), 1.53 (m, 1H), 1.14 (m, 1H), 0.98 (m, 1H), 0.70 (d, J=6.9 Hz, 3H,). 13C NMR (CD3OD) δ 159.5, 149.3, 141.9, 131.4, 130.1, 129.9, 127.9, 117.5, 115.1, 114.9, 113.6, 113.4, 89.9, 57.1, 56.2, 55.8, 55.1, 51.4, 46.8, 45.0, 44.1, 40.1, 38.4, 37.4, 34.0, 30.6, 28.4, 27.4, 18.5. Anal. (C24H34Cl2N2O.H2O) C, H, N.
