NBS (0.052 g, 0.29 mmol) was added in one portion to a solution of (3R,4aR,12bR)-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 (11, R1=4-Fluorophenyl, R2=Ethyl, R3=Trifluoromethyl) (0.100 g, 0.224 mmol) and DMF (2.20 mL) under a nitrogen atmosphere. The solution was warmed to about 60° C. for about 2 h. A solution of NBS (0.0040 g, 0.022 mmol) and DMF (0.10 mL) was added. After about 1 h, a solution of NBS (0.0040 g, 0.022 mmol) and DMF (0.10 mL) was added. After about 30 min, the light yellow solution was allowed to cool to rt. Sat. aq. NaHCO3 (5 mL), water (5 mL), and EtOAc (10 mL) were added. The layers were separated and the organics were washed with water (10 mL) and sat. aq. NaCl (10 mL). The aqueous layers were extracted with EtOAc (10 mL). The combined organics were dried over Na2SO4, filtered, and concentrated. The residue was purified on silica gel (12 g) using a gradient of 0-7% EtOAc in heptane. The fractions containing product were combined and concentrated under reduced pressure to afford a sticky ivory solid. The residue was dissolved in MeCN, treated with water, and concentrated under reduced pressure to remove MeCN. The mixture was frozen then lyophilized to afford (3R,4aR,12bR)-8-bromo-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 (58, R1=4-Fluorophenyl, R2=Ethyl, R3=Trifluoromethyl) (0.0809 g, 69% yield) as a fluffy white solid. LC/MS, method 2, Rt=3.00 min, MS m/z 525 and 527 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.29 (s, 1H), 7.91 (s, 1H), 7.55-7.48 (m, 2H), 7.37-7.29 (m, 2H), 5.87 (s, 1H), 3.73-3.63 (m, 1H), 3.04-2.90 (m, 1H), 2.42-2.27 (m, 1H), 2.22-1.52 (m, 11H), 1.29-1.10 (m, 1H), 0.46 (t, J=7.3 Hz, 3H).
