2-(Tert-butyldimethylsilyloxymethyl)-4-bromothiazole → 1-[2-(tert-butyldimethylsilanyloxymethyl)thiazol-4-yl]-2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]ethanol

Participants

Reaction Steps

To a chilled (−78° C.) solution of 4-bromo-2-(tert-butyldimethylsilanyloxymethyl)thiazole (339 mg, 1.10 mmol) (prepared according to a procedure described by Nicolaou et al., Bioorg. Med. Chem. 1999, 7, 665-697) in dry ether (5 mL) was added n-BuLi (440 μL, 2.5 M in hexane, 1.10 mmol). After 2 minutes, a chilled (−78° C.) solution of 2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]ethanone (308 mg, 1.00 mmol) in 5 mL of dry ether added. After 15 minutes, the mixture was warmed to room temperature and quenched with 20 mL of saturated aqueous ammonium chloride and extracted with three 20 mL portions of diethyl ether. The combined organic layers were washed with 20 mL of brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was chromatographed on SiO2 (0-30% ethyl acetate in hexanes, gradient) to afford 358 mg (67%) of 1-[2-(tert-butyldimethylsilanyloxymethyl)thiazol-4-yl]-2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]ethanol. MS m/z 538.97 (MH+).

Provenance & Evidence