Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[Li]CCCC.[F:13][C:14]1[CH:19]=[CH:18][C:17]([N:20]2[C:28]3[CH:27]=[C:26]4[CH2:29][CH2:30][CH2:31][C@@H:32]5[CH2:37][C@@:36]([O:42][Si](CC)(CC)CC)([C:38]([F:41])([F:40])[F:39])[CH2:35][CH2:34][C@@:33]5([C:50]#N)[C:25]4=[CH:24][C:23]=3[CH:22]=[N:21]2)=[CH:16][CH:15]=1.[F:52][C:53]1[CH:58]=[CH:57][C:56]([N:59]2[C:67]3[CH:66]=[C:65]4[CH2:68][CH2:69][CH2:70][C@@H:71]5[CH2:76][C@@:75]([O:81][Si](CC)(CC)CC)([C:77]([F:80])([F:79])[F:78])[CH2:74][CH2:73][C@@:72]5([C:89]#N)[C:64]4=[CH:63][C:62]=3[CH:61]=[N:60]2)=[CH:55][CH:54]=1>C1COCC1>[F:13][C:14]1[CH:15]=[CH:16][C:17]([N:20]2[C:28]3[CH:27]=[C:26]4[CH2:29][CH2:30][CH2:31][C@@H:32]5[CH2:37][C@@:36]([OH:42])([C:38]([F:39])([F:41])[F:40])[CH2:35][CH2:34][C@@:33]5([C:50]([C:2]5[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=5)=[O:81])[C:25]4=[CH:24][C:23]=3[CH:22]=[N:21]2)=[CH:18][CH:19]=1.[F:52][C:53]1[CH:54]=[CH:55][C:56]([N:59]2[C:67]3[CH:66]=[C:65]4[CH2:68][CH2:69][CH2:70][C@@H:71]5[CH2:76][C@@:75]([OH:81])([C:77]([F:78])([F:80])[F:79])[CH2:74][CH2:73][C@@:72]5([C:89]([C:2]5[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=5)=[O:42])[C:64]4=[CH:63][C:62]=3[CH:61]=[N:60]2)=[CH:57][CH:58]=1
Reactant: Brc1ccccn1
Reactant: CC[Si](CC)(CC)O[C@]1(C(F)(F)F)CC[C@@]2(C#N)c3cc4cnn(-c5ccc(F)cc5)c4cc3CCC[C@@H]2C1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: O=C(c1ccccn1)[C@@]12CC[C@](O)(C(F)(F)F)C[C@H]1CCCc1cc3c(cnn3-c3ccc(F)cc3)cc12
Temperature: -78 °C
Reaction time: 0.25 h

Procedure:
A solution of 2-bromopyridine (506 mg, 3.20 mmol) in THF (6 mL) was cooled to about −78° C. under nitrogen. A solution of BuLi (2.5M solution in hexanes, 1.26 mL, 3.14 mmol) was added dropwise while maintaining reaction temperature below −75° C. The reaction was stirred for about 15 min at about −78° C. then a solution of (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-carbonitrile; compound with (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-carbonitrile (33, R1=4-Fluorophenyl, R3=Trifluoromethyl, Rg=TES) (350 mg, 0.628 mmol) in THF (2.5 mL) was added dropwise maintaining reaction temperature below −74° C. The reaction was stirred for about 30 min and then quenched by addition of 2 N aq. HCl (5 mL). The mixture was stirred about 6 h at rt and then cooled to rt. The reaction was neutralized by addition of sat. aq. NaHCO3 (20 mL) and the products extracted with EtOAc (2×20 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. The product was purified on silica gel (25 g) using a gradient of 25-50% EtOAc in heptane. Product fractions were combined and concentrated under reduced pressure. The residue was dissolved in MeOH (10 mL), water (5 mL) was added and the mixture was concentrated to about 5 mL volume. The product was filtered off and dried under reduced pressure at about 50° C. to yield ((3R,4aR,12bS)-9-(4-fluorophenyl)-3-hydroxy-3-(trifluoromethyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazol-12b-yl)(pyridin-2-yl)methanone compound with ((3R,4aR,12bS)-9-(4-fluorophenyl)-3-hydroxy-3-(trifluoromethyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazol-12b-yl)(pyridin-2-yl)methanone (11, R1=4-Fluorophenyl, R2=2-Pyridylcarbonyl, R3=Trifluoromethyl) (49 mg, 15%) as a yellow solid; Major isomer: LC/MS, method 2, Rt=2.80 min, MS m/z 524 (M+H)+, 1H NMR (400 MHz, DMSO) δ 9.90 (s, 1H), 8.63 (d, J=4.0 Hz, 1H), 8.09-8.02 (m, 1H), 7.94-7.88 (m, 2H), 7.66-7.60 (m, 1H), 7.35-7.29 (m, 2H), 7.25-7.18 (m, 2H), 6.98 (s, 1H), 6.19 (s, 1H), 3.16-3.05 (m, 1H), 2.77-2.65 (m, 1H), 2.19-1.86 (m, 6H), 1.77-1.58 (m, 3H), 1.53-1.39 (m, 1H), 1.37-1.23 (m, 1H). Evidence of two hemi-ketal forms is observed in both the NMR and the LC/MS.