Reaction Steps
A flask with stir bar and nitrogen line was charged with sodium hydride (60 wt % in oil, 0.212 g, 5.31 mmol) and DMSO (9 mL) then the mixture was warmed in an oil bath heated to about 65° C. for about 1 h. The mixture was cooled to rt, diluted with THF (18 mL) then cooled to about 0° C. Trimethylsulfonium iodide (1.084 g, 5.31 mmol) was added then the mixture was stirred for about 15 min. rac-(4aR,12bR)-12b-Ethyl-9-(4-fluorophenyl)-1,4,4a,5,6,7,9,12b-octahydrobenzo[6,7]cyclohepta[1,2-f]indazole-3 (2H)-one (9, R1=4-Fluorophenyl, R2=Ethyl) (0.800 g, 2.125 mmol) was added in one portion then the mixture was stirred and allowed to warm to rt. After stirring overnight the mixture was concentrated under reduced pressure to remove THF. The mixture was partitioned between water (50 mL) and EtOAc (50 mL). The aqueous layer was extracted with EtOAc (25 mL). The combined organics were washed with water (2×25 mL) then brine (25 mL), dried over MgSO4, then filtered. The filtrate was concentrated under reduced pressure then the material was purified on silica gel (40 g) using 0-10% EtOAc in DCM. Product fractions containing the epoxide isomer with the higher Rf (TLC, 95:5 DCM/EtOAc, vis by UV) were collected and concentrated under reduced pressure to yield rac-(2′R,4aR,12bR)-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] (154, R1=4-Fluorophenyl, R2=Ethyl) (0.308 g, 37.1%); LC/MS, method 3, Rt=2.94 min, MS m/z 391 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.26 (d, J=0.8 Hz, 1H), 7.89 (s, 1H), 7.84-7.77 (m, 2H), 7.56 (s, 1H), 7.45-7.36 (m, 2H), 3.26-3.18 (m, 1H), 2.97-2.92 (m, 1H), 2.61-2.54 (m, 2H), 2.24-2.15 (m, 1H), 2.03-1.71 (m, 8H), 1.62-1.58 (m, 1H), 1.39-1.21 (m, 2H), 1.06-1.01 (m, 1H), 0.40 (t, J=7.3 Hz, 3H).
