Reaction Steps
Freshly prepared sodium ethoxide (1 M solution in EtOH, 3.00 mL, 3.00 mmol) was added to a mixture of (4aR,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; compound with (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 (4aR,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 (9, R1=4-Fluorophenyl, R2=Ethyl) (0.750 g, 1.99 mmol), THF (6.50 mL) and EtOH (13.0 mL) under a nitrogen atmosphere. Benzaldehyde (0.220 mL, 2.17 mmol) was added. After about 3 h, sodium ethoxide (1 M solution in EtOH, 3.00 mL, 3.00 mmol) was added. After about 15 h, the mixture was warmed to about 60° C. After about 30 min, the mixture was allowed to cool to rt. AcOH (0.500 mL) was added. The volatiles were removed under reduced pressure. Water (25 mL) and DCM (50 mL) were added. The layers were separated and the organics were washed with sat. aq. NaCl (25 mL) then dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified on silica gel (80 g) using a gradient of 0-25% EtOAc in heptane. The fractions containing product were combined and concentrated under reduced pressure to afford (4aR,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; compound with (4aS,12bS,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 (68, R1=4-Fluorophenyl, R2=Ethyl) (0.545 g, 59% yield) as an ivory solid. LC/MS, method 3, Rt=3.05 min, MS m/z 465 (M+H)+. 1H NMR (400 MHz, DMSO) δ 7.98 (s, 1H), 7.81-7.74 (m, 2H), 7.67-7.62 (m, 2H), 7.62-7.53 (m, 4H), 7.53-7.45 (m, 2H), 7.44-7.35 (m, 2H), 3.37-3.32 (m, 2H), 3.28-3.17 (m, 1H), 2.98-2.87 (m, 1H), 2.62-2.43 (m, 2H), 2.38-2.25 (m, 1H), 2.16-1.89 (m, 3H), 1.75-1.64 (m, 1H), 1.51-1.23 (m, 2H), 0.19 (t, J=7.2 Hz, 3H).
