Reaction Steps
To a solution of 5-(naphthalen-2-yl)bicyclo[3.1.0]hexan-2-one (0.72 g, 3.24 mmol) in methanol (50 mL) was added dimethylamine (2M in tetrahydrofuran; 6.48 mL, 12.96 mmol, 4 eq.) and sodium cyanoborohydride (0.26 g, 4.21 mmol, 1.3 eq). The mixture was stirred at room temperature overnight. The reaction mixture was cooled to 10° C., and acidified with 1N HCl (25 mL). The reaction mixture was concentrated at 30° C. and the resulting aqueous layer diluted with water (25 mL). The aqueous layer was then extracted with ethyl acetate (125 mL) to remove nonpolar impurities. The aqueous layer was then adjusted to pH 9 with 1N NaOH (25 mL), and the aqueous layer extracted with ethyl acetate (3×25 mL). The combined organic layers were dried over magnesium sulphate, filtered and concentrated in vacuo. The residue was then dissolved in diethyl ether (20 mL) and the HCl salt was formed by slowly adding HCl/diethyl ether solution (10 mL). The slurry was stirred for 30 mins before filtration. The solids were rinsed with ice cold diethyl ether (10 mL) and the compound was quickly transferred to a vacuum oven and dried for 12 hours to afford the desired compound (0.81 g, 28%) as a white solid. 1H NMR (400 MHz, CD3OD) δ ppm 1.18-1.21 (1H, m, CH), 1.43-1.46 (1H, m, CH), 1.57-1.61 (1H, m, CH), 2.14-2.19 (1H, m, CH), 2.27-2.36 (2H, m, CH2), 2.37-2.43 (1H, m, CH), 2.92 (3H, s, CH3), 3.06 (3H, s, CH3), 4.04-4.09 (1H, m, CH), 7.34 (1H, dd, J=1.9, 8.4, ArH), 7.39-7.47 (2H, m, ArH), 7.71-7.72 (1H, m, ArH), 7.79-7.80 (3H, m, ArH). 13C NMR (400 MHz, CD3OD); δ ppm 13.74 (s, 1C), 24.28 (s, 1C), 25.31 (s, 1C), 30.70 (s, 1C), 33.53 (s, 1C), 41.58 (s, 1C), 41.89 (s, 1C), 69.80 (s, 1C), 124.50 (s, 1C), 124.75 (s, 1C), 125.33 (s, 1C), 125.93 (s, 1C), 127.25 (s, 1C), 127.87 (s, 1C), 132.35 (s, 1C), 133.57 (s, 1C), 140.02 (s, 1C). LCMS (M+1) 252.
