Reaction Steps
CsF (0.050 g, 0.33 mmol) was added to a mixture of (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) (0.617 g, 1.33 mmol) and DME (13.0 mL) under nitrogen. After stirring for about 15 min, the mixture was cooled to about 0° C. (Trifluoromethyl)trimethylsilane (0.300 mL, 2.03 mmol) was added dropwise. After about 45 min, the ice bath was removed and the volatiles were removed under reduced pressure. DME (13.0 mL) was added. TBAF (1 M solution in THF, 1.50 mL, 1.50 mmol) was added in one portion. After about 1 h, water (25 mL) and EtOAc (25 mL) were added. The layers were separated and the organics were washed with water (2×25 mL) then dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified on silica gel (40 g) using a gradient of 0-20% EtOAc in heptane. The fractions containing product were combined and concentrated under reduced pressure to afford (3R,4aS,12bS,E)-2-Benzylidene-12b-ethyl-9-(4-fluorophenyl)-3-(trifluoromethyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazol-3-ol; compound with (3S,4aR,12bR,E)-2-benzylidene-12b-ethyl-9-(4-fluorophenyl)-3-(trifluoromethyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazol-3-ol (69, R1=4-Fluorophenyl, R2=Ethyl, R3=Trifluoromethyl) (0.489 g, 69% yield) as an ivory solid. LC/MS, method 3, Rt=3.03 min, MS m/z 535 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.27 (d, J=0.8 Hz, 1H), 7.86 (s, 1H), 7.83-7.72 (m, 2H), 7.51 (s, 1H), 7.46-7.34 (m, 6H), 7.31-7.23 (m, 1H), 7.21-7.17 (m, 1H), 6.29 (s, 1H), 3.56-3.45 (m, 1H), 3.11-2.99 (m, 1H), 2.93-2.81 (m, 1H), 2.70-2.59 (m, 1H), 2.17-1.89 (m, 4H), 1.86-1.60 (m, 3H), 1.52-1.23 (m, 2H), −0.21 (t, J=7.2 Hz, 3H).
