Reaction Steps
A solution of (3R,4aR,12bS)-9-(4-fluorophenyl)-3-((triethylsilyl)oxy)-3-(trifluoromethyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazole-12b-carbonitrile; compound with (3S,4aS,12bR)-9-(4-fluorophenyl)-3-((triethylsilyl)oxy)-3-(trifluoromethyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazole-12b-carbonitrile (39, R1=4-Fluorophenyl, R3=Trifluoromethyl) (600 mg, 1.08 mmol) in Toluene (24 mL) was cooled to about 0° C. and DIBAL-H (1M solution in cyclohexane, 6.5 mL, 6.5 mmol) was added dropwise while maintaining the reaction temperature below about 1° C. The reaction was stirred at about 0° C. for about 1 h. The reaction was quenched by addition of 6% HOAc in sat. aq. NaOAc (25 mL) while maintaining the reaction temperature below 5° C. The mixture was allowed to warm to rt, water (10 mL) was added and stirring was continued for about 2 h. The layers were separated and the organic layer was stirred with sat. aq. NH4Cl (25 mL) for about 2 h. The organic layer was dried with Na2SO4, filtered and concentrated to a waxy solid (730 mg). The crude was purified on silica gel (40 g) using a gradient of 5-20% EtOAc in heptane. Product fractions were combine and concentrated under reduced pressure to yield (3R,4aR,12bS)-9-(4-fluorophenyl)-3-((triethylsilyl)oxy)-3-(trifluoromethyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazole-12b-carbaldehyde; compound with (3S,4aS,12bR)-9-(4-fluorophenyl)-3-((triethylsilyl)oxy)-3-(trifluoromethyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazole-12b-carbaldehyde (40, R1=4-Fluorophenyl, R3=Trifluoromethyl) as a viscous oil (566 mg, 94%); LC/MS, method 4, Rt=2.58 min, MS m/z 561 (M+H)+, 1H NMR (400 MHz, DMSO) δ 9.37 (d, J=1.9 Hz, 1H), 8.32 (d, J=0.9 Hz, 1H), 8.04 (s, 1H), 7.82-7.77 (m, 2H), 7.63 (s, 1H), 7.44-7.37 (m, 2H), 3.00-2.91 (m, 1H), 2.71-2.58 (m, 1H), 2.29-1.90 (m, 6H), 1.86-1.58 (m, 4H), 1.36-1.21 (m, 1H), 0.99-0.90 (m, 9H), 0.67-0.58 (m, 6H).
