Reaction Steps
NBS (0.011 g, 0.064 mmol) was added to a solution of (3R,4aR,12bS)-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 (15, R1=4-Fluorophenyl, R2=Ethyl, R3=Trifluoromethyl) (0.022 g, 0.049 mmol) in DMF (0.5 mL) and the mixture was heated to about 60° C. for about 3 h. After cooling to rt, the reaction was quenched with ice (5 g). Sat. Aq. Na2CO3 (10 mL) and EtOAc (20 mL) were added. The layers were separated and the organic layer was washed with water (10 mL) then dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified on silica gel (4 g) using a gradient of 0-27% EtOAc in heptane. Product fractions were combined and concentrated under reduced pressure. The residue was lyophilized to yield (3R,4aR,12bS)-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 (46, R1=4-Fluorophenyl, R2=Ethyl, R3=Trifluoromethyl) (0.013 g, 49% yield); LC/MS, method 2, Rt=3.13 min.; MS m/z: 525 and 527 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.29 (s, 1H), 7.90 (s, 1H), 7.57-7.50 (m, 2H), 7.38-7.30 (m, 2H), 5.56 (s, 1H), 3.56-3.44 (m, 1H), 3.03-2.88 (m, 1H), 2.43-2.18 (m, 2H), 2.16-1.66 (m, 7H), 1.64-1.38 (m, 4H), 0.68 (t, J=7.3 Hz, 3H).
