2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]ethanone → 2,2,2-Trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-(1H-indazol-3-yl)ethanol

Participants

Reaction Steps

To a chilled (−78° C.) solution of 97 mg (0.49 mmol) of 3-bromo-1H-indazole in 5 mL of anhydrous ether was added 195 μL (0.49 mmol) of a 2.5 M solution of n-BuLi in hexanes dropwise. After 5 minutes, 590 μL (1.0 mmol) of a 1.7 M solution of tert-BuLi in pentane was added dropwise. The mixture stirred for 15 minutes and then a solution of 151 mg (0.49 mmol) of 2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]ethanone in 3 mL of ether was added dropwise. After 1 hour, the reaction was monitored by thin layer chromatography (30% ethyl acetate-hexanes) and LCMS. The mixture was diluted with 10 mL of saturated aqueous ammonium chloride and extracted with three 10 mL portions of ethyl acetate. The combined organic layers were washed with three 10 mL portions of brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude residue was chromatographed on silica gel using dichloromethane-hexanes (1:1) to load the sample and then eluting with dichloromethane-hexanes (1:1, then 100:0) followed by ethyl acetate-hexanes (2:8). The material from the column was triturated with ether-hexanes to afford 41 mg (19%) of the title compound. MS m/z 427.20 (MH+).

Provenance & Evidence