Reaction Steps
A flask with stir bar and nitrogen line was charged with sodium hydride (60% in oil 0.106 g, 2.66 mmol) and DMSO (7 mL). The mixture was warmed in an oil bath heated to about 65° C. for about 45 min. The mixture was cooled to rt, diluted with THF (7 mL) then cooled to about 0° C. Trimethylsulfoxonium iodide (0.585 g, 2.66 mmol) was added and the mixture was stirred for about 15 min. (4aR,12bR)-12b-Ethyl-9-(4-fluoro-phenyl)-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 (4aS,12bS)-12b-ethyl-9-(4-fluoro-phenyl)-1,2,4a,5,6,7,9,12b-octahydro-4H-9,10-diaza-benzo[3,4]cyclohepta[1,2-f]inden-3-one (9, R1=4-Fluorophenyl, R2=Ethyl) (0.500 g, 1.328 mmol) suspended in THF (9 mL) was added to the reaction mixture. After about 15 min the ice bath was removed and the mixture was allowed to warm to rt for about 6 h. The mixture was concentrated under reduced pressure and the residue was partitioned between EtOAc (100 mL) and water (50 mL). The layers were separated and the aqueous layer was extracted with EtOAc (25 mL). The combined organic layers were washed with water (2×50 mL) and brine (30 mL). The organic solution was dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified on silica gel (25 g) using a gradient of 0-20% EtOAc in DCM. Product fractions were combined and concentrated under reduced pressure to yield rac-(2′R,4aS,12bS)-12b-ethyl-9-(4-fluorophenyl)-2,4,4a,5,6,7,9,12b-octahydro-1H-spiro[benzo[6,7]cyclohepta[1,2-f]indazole-3,2′-oxirane] (14, R1=4-Fluorophenyl, R2=Ethyl) (0.462 g, 1.183 mmol, 89% yield); LC/MS, method 3, Rt=3.14 min, MS m/z 391 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.27 (d, J=0.8 Hz, 1H), 7.93 (s, 1H), 7.85-7.78 (m, 2H), 7.56 (s, 1H), 7.45-7.37 (m, 2H), 3.26-3.19 (m, 1H), 2.97-2.92 (m, 1H), 2.67 (d, J=4.7 Hz, 1H), 2.62 (d, J=4.7 Hz, 1H), 2.36-2.32 (m, 1H), 2.23-2.14 (m, 1H), 2.12-1.91 (m, 4H), 1.91-1.68 (m, 3H), 1.62-1.54 (m, 1H), 1.32-1.28 (m, 1H), 1.26-1.16 (m, 1H), 1.07-0.94 (m, 1H), 0.40 (t, J=7.3 Hz, 3H).
