Reaction Steps
A 100 mL round-bottom flask equipped with rubber septum and nitrogen inlet needle was charged with sodium hydride (60 wt % in oil, 0.212 g, 5.29 mmol) in DMSO (13 mL) and then the mixture was heated at about 60° C. in a heating block for about 30 min. The mixture was allowed to cool to rt, at which point trimethylsulfoxonium iodide (1.16 g, 5.29 mmol) was added in one portion and the reaction mixture was stirred for about 15 min. A solution of rac-(4aR,12bS)-12b-ethyl-9-(2-methylpyridin-4-yl)-4,4a,5,6,9,12b-hexahydro-1H-benzo[4,5]oxepino[3,2-f]indazol-3 (2H)-one (92, R1=2-methylpyridin-4-yl, R2=Ethyl) (0.993 g, 2.64 mmol) in THF (13 mL) was added in one portion. After about 30 min the reaction was concentrated under reduced pressure and the residue was partitioned between EtOAc (50 mL) and water (50 mL). The layers were separated and the aqueous phase was extracted with EtOAc (2×10 mL). The combined organic phases were washed with brine (50 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The material was purified on silica gel (40 g, EtOAc). Collection and concentration of the appropriate fractions gave rac-(2′R,4aS,12bR)-12b-ethyl-9-(2-methylpyridin-4-yl)-1,2,4,4a,5,6,9,12b-octahydrospiro[benzo[4,5]oxepino[3,2-f]indazole-3,2′-oxirane] (93, R1=2-methylpyridin-4-yl, R2=Ethyl) (0.844 g, 82%). LC/MS, method 3, Rt=2.40 min, MS m/z 390 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 8.61-8.55 (m, 1H), 8.23 (s, 1H), 7.91-7.76 (m, 2H), 7.69 (s, 1H), 7.56 (s, 1H), 4.43-4.31 (m, 1H), 3.84-3.71 (m, 1H), 2.98-2.70 (m, 3H), 2.71-2.56 (m 2H), 2.56-2.16 (m, 4H), 2.07-1.93 (m, 1H), 1.93-1.77 (m, 1H), 1.73-1.33 (m, 4H), 0.97-0.83 (m, 1H), 0.74-0.56 (t, J=7.5 Hz, 3H).
