Reaction Steps
t-Butanol (20 mL) and water (4 mL) were added to rac-(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-carb aldehyde (40, R1=4-Fluorophenyl, R3=Trifluoromethyl) (0.360 g, 0.642 mmol). After cooling to about 0° C., sodium dihydrogenphosphate (0.770 g, 6.42 mmol), 2-methyl-but-2-ene (0.270 g, 3.85 mmol), and sodium chlorite (0.348 g, 3.85 mmol) were added sequentially. After about 30 min, the ice bath was removed and the reaction was allowed to warm to rt. After about 3 h, a 1:1 solution of sat. aq. Na2SO3 and sat. aq. NaCl (50 mL) was added. Water (30 mL) was added. The mixture was extracted with EtOAc (3×50 mL). The combined organics were dried over MgSO4, 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 product fractions were combined and concentrated under reduced pressure to give rac-(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-carboxylic acid (43, R1=4-Fluorophenyl, R3=Trifluoromethyl) (0.267 g, 72% yield); LC/MS, method 4, Rt=2.39 min.; MS m/z: 577 (M+H)+. 1H NMR (400 MHz, DMSO) δ 12.57 (s, 1H), 8.26 (d, J=0.7 Hz, 1H), 7.90 (s, 1H), 7.82-7.75 (m, 2H), 7.54 (s, 1H), 7.45-7.35 (m, 2H), 2.95-2.71 (m, 2H), 2.60-2.48 (m, 1H), 2.42-2.15 (m, 4H), 2.03-1.78 (m, 3H), 1.73-1.52 (m, 2H), 1.34-1.20 (m, 1H), 0.99-0.90 (m, 9H), 0.69-0.59 (m, 6H).
