Reaction Steps
A suspension of 2-methyl-5-[(Z)-2-(6-methylpyridin-3-yl)vinyl]-6,7,8,9,10,11-hexahydro-5H-7,11-epiminocycloocta[b]indole (750 mg, 2.18 mmol; from Example 118B) and platinum(IV) oxide (105 mg, 0.462 mmol; Aldrich) in 2-propanol (30 mL) was heated to 65° C. under hydrogen balloon atmosphere (1 atm) for 16 hours, then cooled to room temperature. The catalyst and solvent were removed, and the residue was purified by preparative chiral supercritical fluid chromatography (ChiralPak® OD-H 5 μm column, 21×250 mm, 35° C., 10-50% gradient of CH3OH—CO2 containing 0.1% diethylamine, flow rate 40 mL/minute, 20 minutes) to afford the title compound as the first-eluting enantiomer: 1H NMR (300 MHz, CDCl3) δ ppm 0.96-1.14 (m, J=18, 18, 9, 5 Hz, 1H), 1.25-1.40 (m, 2H), 1.60 (dd, J=13, 2 Hz, 1H), 1.75-1.96 (m, 2H), 2.03 (d, J=17 Hz, 1H), 2.39 (s, 3H), 2.42 (s, 3H), 2.87 (dd, J=17, 7 Hz, 1H), 3.00-3.21 (m, 2H), 3.43 (t, J=6 Hz, 1H), 4.20-4.42 (m, 3H), 6.92 (dd, J=8, 1 Hz, 1H), 7.09-7.15 (m, 2H), 7.20 (d, J=8 Hz, 1H), 7.36 (dd, J=8, 2 Hz, 1H), 7.88 (d, J=2 Hz, 1H); MS (DCI/NH3) m/z 346 (M+H)+.
