Reaction Steps
A mixture of sodium hydride (60 wt % in oil, 0.038 g, 1.594 mmol) and DMSO (5 mL) was heated to about 65° C. for about 30 min then cooled to rt and diluted with THF (2.5 mL). The reaction mixture was cooled in an ice water bath and trimethyl sulfoxonium iodide (0.149 g, 0.68 mmol) was added then stirred for about 15 min. (4aS,12bS)-12b-ethyl-9-(4-fluorophenyl)-1,4,4a,5,6,7,9,12b-octahydrobenzo[6,7]cyclohepta[1,2-f]indazol-3 (2H)-one (10, R1=4-Fluorophenyl, R2=Ethyl) was then added in one portion dissolved in THF (2.5 mL) and the mixture was stirred to rt for about 5 h. The solvents were removed and the residue was diluted with about 15 mL water and extracted with EtOAc (15 mL×3). The combined organics were washed with sat. aq. NaCl (15 mL). The organic layer was dried over MgSO4 filtered and concentrated to about 220 mg of a crude viscous oil. The sample was further purified on silica gel (12 g) using DCM/EtOAc with ramp conditions of 0-100% EtOAc in DCM over 20 min followed by 10 min at 100% EtOAc. The product fractions were concentrated to colorless viscous dried on a high vacuum to yield (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) (131 mg,50%) of a white crystalline solid. LC/MS, method 4, Rt=2.08 min, MS m/z 391 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.27 (s, 1H), 7.93 (s, 1H), 7.85-7.77 (m, 2H), 7.56 (s, 1H), 7.45-7.36 (m, 2H), 4.03 (q, J=7.1 Hz, 1H), 3.25-3.17 (m, 1H), 3.00-2.90 (m, 1H), 2.67 (d, J=4.7 Hz, 1H), 2.62 (d, J=4.7 Hz, 1H), 2.38-2.30 (m, 1H), 2.25-1.92 (m, 3H), 1.93-1.67 (m, 3H), 1.62-1.53 (m, 1H), 1.40-1.24 (m, 1H), 1.18 (t, J=7.1 Hz, 2H), 1.04-0.95 (m, 1H), 0.40 (t, J=7.3 Hz, 3H). Sign of rotation is negative.
