Reaction Steps
Sodium (0.092 g, 4.0 mmol) was added to ethanol (20 mL) and mixed at rt until the sodium was completely consumed. A solution of rac-(4aS,12bR)-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) (1.00 g, 2.66 mmol) in THF (10 mL) was added in one portion. Benzaldehyde (0.310 g, 2.92 mmol) was added and the reaction mixture was stirred at rt for about 3 h. The organic volatiles were removed under reduced pressure. The residue was partitioned between EtOAc (70 mL) and water (50 mL). The organic layer was dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified on silica gel (40 g) using a gradient of 5-18% EtOAc in heptane. The product fractions were combined and concentrated under reduced pressure to give rac-(4aS,12bR,E)-2-benzylidene-12b-ethyl-9-(4-fluorophenyl)-1,4,4a,5,6,7,9,12b-octahydrobenzo[6,7]cyclohepta[1,2-f]indazol-3(2H)-one (53, R1=4-Fluorophenyl, R2=Ethyl) (1.00 g, 81% yield); LC/MS, method 3, Rt=3.11 min.; MS m/z: 465 (M+H)+. 1H NMR (400 MHz, DMSO) δ 7.98-7.96 (m, 1H), 7.80-7.73 (m, 2H), 7.73-7.67 (m, 2H), 7.62-7.55 (m, 3H), 7.53-7.46 (m, 2H), 7.44-7.35 (m, 2H), 6.99 (s, 1H), 3.72-3.62 (m, 1H), 3.27-3.15 (m, 1H), 3.01-2.91 (m, 1H), 2.90-2.81 (m, 1H), 2.58-2.52 (m, 1H), 2.48-2.37 (m, 1H), 2.36-2.25 (m, 1H), 2.25-2.14 (m, 1H), 2.11-1.97 (m, 1H), 1.87-1.45 (m, 4H), 0.65 (t, J=7.3 Hz, 3H).
