Hydrochloric Acid → 2,2,2-Trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-thiazol-5-ylethanol

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Reaction Steps

To a chilled (−78° C.) solution of 2-trimethylsilanyl-thiazole (157 mg, 1.00 mmol) in dry ether (2 mL) was added n-BuLi (440 μL, 2.5 M in hexanes, 1.10 mmol). After 30 minutes, a solution of 2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]ethanone (154 mg, 0.50 mmol) in dry ether (2 mL) was added. After 1 hour, the mixture was warmed to room temperature, quenched with 10 mL of saturated aqueous sodium bicarbonate and extracted with three 10 mL portions of ethyl ether. The combined organic layers was washed with 10 mL of brine, dried over sodium sulfate, filtered, and concentrated in vacuo to give 202 mg of the crude product. To a solution of crude product (100 mg) in THF (2 mL) was added 2 M HCl (1 mL) and the mixture was stirred overnight. The mixture was then quenched with 10 mL of saturated aqueous sodium bicarbonate and extracted with three 10 mL portions of ethyl acetate. The combined organic layers were washed with brine (10 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo. The mixture was purified over SiO2 using ethyl acetate-hexanes (0-100% gradient) to afford 38.4 mg (39% over two steps) of the title compound. MS m/z 394.26 (MH+).

Provenance & Evidence