(Trifluoromethyl)trimethylsilane → 1,1,1-Trifluoro-4-(1-(4-fluorophenyl)-1h-indazol-5-yl)-2,3,3-trimethyl-4-phenylbutan-2-ol

Participants

Reaction Conditions

Reaction Steps

To a solution of the compound of Example 120, 4-(1-(4-fluorophenyl)-1H-indazol-5-yl)-3,3-dimethyl-4-phenylbutan-2-one (12 mg, 0.031 mmol) in THF (1 ml) at 0° C. was added trimethyl(trifluoromethyl)silane (22 mg, 0.155 mmol) and tetrabutylammonium fluoride in THF (0.031 ml, 0.031 mmol, 1M THF solution). The reaction mixture was stirred at 0° C. for 10 minutes, and then at room temperature for 45 minutes. Additional trimethyl(trifluoromethyl)silane (22 mg, 0.155 mmol) was added to the reaction mixture, after which stirring was continued for 2 hours. The reaction was quenched with saturated NH4Cl and extracted with ethyl acetate. The organic phase was washed with brine, dried over MgSO4 and concentrated to give the crude product. The crude material was purified via chromatography on silica gel eluting with 10% ethyl acetate in hexane to afford the compound of Example 135 as a white solid (10 mg, 71% yield). It is a mixture of diastereomers in 1:1 ratio. 1H NMR (400 MHz, MeOD) δ ppm 8.17 (1 H, s) 7.98 (1 H, d, J=16.79 Hz) 7.68 (3 H, dd, J=8.90, 4.83 Hz) 7.58 (2 H, d, J=8.14 Hz) 7.54 (1 H, d, J=7.63 Hz) 7.20-7.33 (4 H, m) 7.12 (1 H, t, J=7.12 Hz) 4.55 (1 H, d, J=5.09 Hz) 1.31 (3 H, 2 singlets) 1.22 (3 H, 2 singlets) 1.13 (3 H, 2 singlets). LC/MS (m/z) 387.20 [(M+H)+]; HPLC Rt: 3.758 min.

Provenance & Evidence