Reaction Steps
rac-(4aR,13bS)-9-(4-Fluorophenyl)-13 b-(pyridin-2-ylmethyl)-4,4a,5,6,7,13 b-hexahydro-1H-benzo[3,4]cyclohepta[1,2-d][1,2,3]triazolo[1,5-a]pyridin-3 (2H)-one (157, R1=4-Fluorophenyl, R2=Pyridin-2-ylmethyl) (0.139 g, 0.316 mmol) was suspended in DME (3 mL) and CsF (0.029 g, 0.19 mmol) was added. The mixture was cooled to about −10° C. then trimethyl(trifluoromethyl)silane (0.093 mL, 0.63 mmol) was added. After stirring overnight, TBAF (1 M in THF) (0.316 mL, 0.316 mmol) was added and the mixture was allowed to warm to rt. The mixture was concentrated under reduced pressure then the residue was purified on silica gel (12 g) using a gradient of 10-85% EtOAc in heptane. Product fractions were combined and concentrated under reduced pressure and then triturated with EtOAc to provide rac-(3R,4aR,13bS)-9-(4-fluorophenyl)-13b-(pyridin-2-ylmethyl)-3-(trifluoromethyl)-2,3,4,4a,5,6,7,13b-octahydro-1H-benzo[3,4]cyclohepta[1,2-d][1,2,3]triazolo[1,5-a]pyridin-3-ol (158, R1=4-Fluorophenyl, R2=Pyridin-2-ylmethyl, R3=Trifluoromethyl) (0.031 g, 20%); LC/MS, method 2, Rt=2.45 min, MS m/z 511 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.39 (s, 1H), 8.34-8.29 (m, 1H), 8.11 (s, 1H), 8.08-8.02 (m, 2H), 7.40-7.30 (m, 3H), 7.06-7.00 (m, 1H), 6.52-6.47 (m, 1H), 5.97 (s, 1H), 3.67 (d, J=13.4 Hz, 1H), 3.56-3.42 (m, 1H), 3.27-3.15 (m, 2H), 2.22-2.07 (m, 2H), 2.07-1.67 (m, 7H), 1.55-1.38 (m, 1H), 1.30-1.20 (m, 1H).
