Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[CH:15]=[C:14]4[CH2:17][CH2:18][CH2:19][C@H:20]5[CH2:25][C@:24]([OH:30])([C:26]([F:29])([F:28])[F:27])[CH2:23][CH2:22][C@:21]5([CH2:31][CH:32]=O)[C:13]4=[CH:12][C:11]=3[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[F:34][C:35]1[CH:40]=[CH:39][C:38]([N:41]2[C:49]3[CH:48]=[C:47]4[CH2:50][CH2:51][CH2:52][C@@H:53]5[CH2:58][C@@:57]([OH:63])([C:59]([F:62])([F:61])[F:60])[CH2:56][CH2:55][C@@:54]5([CH2:64][CH:65]=O)[C:46]4=[CH:45][C:44]=3[CH:43]=[N:42]2)=[CH:37][CH:36]=1.Cl.NO.C(OC(=O)C)(=O)C>N1C=CC=CC=1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[CH:15]=[C:14]4[CH2:17][CH2:18][CH2:19][C@H:20]5[CH2:25][C@:24]([OH:30])([C:26]([F:28])([F:27])[F:29])[CH2:23][CH2:22][C@:21]5([CH2:31][C:32]#[N:41])[C:13]4=[CH:12][C:11]=3[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[F:34][C:35]1[CH:40]=[CH:39][C:38]([N:41]2[C:49]3[CH:48]=[C:47]4[CH2:50][CH2:51][CH2:52][C@@H:53]5[CH2:58][C@@:57]([OH:63])([C:59]([F:61])([F:60])[F:62])[CH2:56][CH2:55][C@@:54]5([CH2:64][C:65]#[N:8])[C:46]4=[CH:45][C:44]=3[CH:43]=[N:42]2)=[CH:37][CH:36]=1
Reactant: O=CC[C@]12CC[C@@](O)(C(F)(F)F)C[C@@H]1CCCc1cc3c(cnn3-c3ccc(F)cc3)cc12
Reactant: O=CC[C@@]12CC[C@](O)(C(F)(F)F)C[C@H]1CCCc1cc3c(cnn3-c3ccc(F)cc3)cc12
Agent: Cl
Agent: NO
Solvent: CC(=O)OC(C)=O
Solvent: c1ccncc1
Product: N#CC[C@@]12CC[C@](O)(C(F)(F)F)C[C@H]1CCCc1cc3c(cnn3-c3ccc(F)cc3)cc12
Product: N#CC[C@]12CC[C@@](O)(C(F)(F)F)C[C@@H]1CCCc1cc3c(cnn3-c3ccc(F)cc3)cc12
Temperature: 60 °C
Yield: 79 %

Procedure:
A solution of 2-((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)acetaldehyde; compound with 2-((3S,4aS,12bR)-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)acetaldehyde (41, R1=4-Fluorophenyl, R3=Trifluoromethyl) (320 mg, 0.695 mmol) in pyridine (10 mL) was treated with hydroxylamine hydrochloride (53 mg, 0.76 mmol) and the mixture was heated to about 60° C. for about 15 min, then cooled to rt. Acetic anhydride (0.33 mL, 3.47 mmol) was added dropwise then the mixture was heated to about 60° C. for about 3 h. The reaction was cooled and concentrated under reduced pressure. The residue was dissolved in EtOAc (25 mL) and washed with 2N aq. NaOH and 2N aq. HCl. The organic layer was dried over Na2SO4 and filtered. Silica gel (˜2 g) was added and the solvent removed under reduced pressure. The residue was purified on silica gel (12 g) using a gradient of 10-50% EtOAc in heptane as eluant. Product fractions were combined and concentrated under reduced pressure to yield 2-((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)acetonitrile; compound with 2-((3S,4aS,12bR)-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)acetonitrile (42, R1=4-Fluorophenyl, R3=Trifluoromethyl) as a foam (255 mg, 79%); LC/MS, method 4, Rt=1.69 min, MS m/z 458 (M+H)+, 1H NMR (400 MHz, DMSO) δ 8.29 (d, J=0.8 Hz, 1H), 7.99 (s, 1H), 7.83-7.75 (m, 2H), 7.61 (s, 1H), 7.44-7.36 (m, 2H), 5.93 (s, 1H), 3.37 (d, J=17.4 Hz, 1H), 3.28-3.27 (m, 1H), 3.10 (d, J=17.4 Hz, 1H), 3.05-2.94 (m, 1H), 2.41-2.29 (m, 1H), 2.26-2.16 (m, 1H), 2.10-2.01 (m, 1H), 2.01-1.92 (m, 1H), 1.87-1.55 (m, 6H), 1.42-1.29 (m, 1H).