Reaction Steps
Sodium hydride (60 wt % in oil, 0.454 g, 11.35 mmol) and DMSO (25 mL) were heated to about 65° C. for about 30 min then cooled to rt. THF (50 mL) was added then the mixture was cooled to about 0° C. Trimethylsulfoxonium iodide (2.56 g, 11.63 mmol) was added then after about 30 min rac-(4aR,12bR)-9-(4-fluorophenyl)-12b-(pyridin-2-ylmethyl)-1,4,4a,5,6,7,9,12b-octahydrobenzo[3,4]cyclohepta[1,2-b]pyrazolo[4,3-e]pyridin-3 (2H)-one (118, R1=4-Fluorophenyl, R2=Pyridin-2-ylmethyl) (2.5 g, 5.68 mmol) was added. The mixture was allowed to warm to rt and stir for about 12 h. The mixture was concentrated under reduced pressure then the material was partitioned between water (100 mL) and EtOAc (50 mL). The aqueous layer was extracted with EtOAc (25 mL) then the organic solutions were combined and washed with water (75 mL) then brine (30 mL), dried over MgSO4 then filtered. The filtrate was concentrated under reduced pressure and the material was purified on silica gel (120 g) using a gradient from 0-10% MeOH in DCM. Product fractions were combined 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[3,4]cyclohepta[1,2-b]pyrazolo[4,3-e]pyridine-3,2′-oxirane] (119, R1=4-Fluorophenyl, R2=Pyridin-2-ylmethyl) (1.865 g, 72.3%); LC/MS, method 3, Rt=2.65 min, MS m/z 455 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.42-8.34 (m, 2H), 8.32-8.28 (m, 1H), 8.20 (s, 1H), 7.75-7.72 (m, 1H), 7.49-7.37 (m, 3H), 7.06 (ddd, J=5.2, 4.5, 0.9 Hz, 1H), 6.72-6.67 (m, 1H), 3.73 (d, J=12.8 Hz, 1H), 3.59-3.47 (m, 1H), 3.42-3.33 (m, 1H), 3.02 (d, J=12.9 Hz, 1H), 2.70-2.56 (m, 1H), 2.44-2.34 (m, 2H), 2.13-2.00 (m, 1H), 1.96-1.81 (m, 2H), 1.79-1.58 (m, 3H), 1.35-1.21 (m, 3H), 1.21-1.10 (m, 1H).
