Reaction Steps
A flask with stir bar and nitrogen line was charged with DMSO (2 mL) and sodium hydride (60 wt % in oil, 0.021 g, 0.523 mmol). The mixture was warmed in an oil bath heated to about 65° C. for about 30 min then cooled to rt. THF (1 mL) was added and the mixture was cooled to about 0° C. Trimethylsulfoxonium iodide (0.115 g, 0.523 mmol) was added and the mixture was stirred for about 15 min. (4aS,12bS)-9-(4-Fluorophenyl)-12b-pyridin-2-ylmethyl-1,2,4a,5,6,7,9,12b-octahydro-4H-9,10-diaza-benzo[3,4]cyclohepta[1,2-f]inden-3-one; compound with (4aR,12bR)-9-(4-fluoro-phenyl)-12b-pyridin-2-ylmethyl-1,2,4a,5,6,7,9,12b-octahydro-4H-9,10-diaza-benzo[3,4]cyclohepta[1,2-f]inden-3-one (10, R1=4-Fluorophenyl, R2=Pyridin-2-ylmethyl) (0.115 g, 0.262 mmol) in THF (3 mL) was added and the mixture was allowed to warm to rt for about 18 h. The mixture was diluted with EtOAc (25 mL) and washed with water (25 mL). The aqueous layer was extracted with EtOAc (25 mL) then the combined organic layers were washed with water (2×25 mL) and brine (25 mL), dried over MgSO4, filtered and concentrated under reduced pressure to yield rac-(2′R,4aS,12bS)-9-(4-fluorophenyl)-12b-(pyridin-2-ylmethyl)-2,4,4a,5,6,7,9,12b-octahydro-1H-spiro[benzo[6,7]cyclohepta[1,2-f]indazole-3,2′-oxirane] (R1=4-Fluorophenyl, R2=Pyridin-2-ylmethyl) (0.115 g, 97%); LC/MS, method 3, Rt=2.63 min, MS m/z 454 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.37-8.35 (m, 1H), 8.14 (d, J=0.7 Hz, 1H), 7.85-7.77 (m, 2H), 7.65 (s, 1H), 7.44-7.32 (m, 4H), 7.08-7.04 (m, 1H), 6.48 (d, J=7.8 Hz, 1H), 3.61 (d, J=12.7 Hz, 1H), 3.34-3.26 (m, 1H), 3.13-3.06 (m, 1H), 3.01 (d, J=12.8 Hz, 1H), 2.60-2.43 (m, 1H), 2.39-2.25 (m, 2H), 2.21-2.12 (m, 1H), 1.87-1.78 (m, 2H), 1.75-1.56 (m, 3H), 1.54-1.50 (m, 1H), 1.28-1.19 (m, 1H), 1.17-1.09 (m, 1H), 0.88-0.74 (m, 1H).
