Tetrahydrofuran → HCID 86682359, compound

Participants

Reaction Steps

A 1.0 M solution of lithium hexamethyldisilazide in tetrahydrofuran (7.55 mL, 7.55 mmol) was added to a solution of 4-fluoro-2-pyridazin-4-yl-5-(trifluoromethyl)phenol (Preparation 11, 1.30 g, 5.04 mmol) in N,N-dimethylformamide (30 mL). After stirring for 5 minutes, tert-butyl-[(5-chloro-2,4-difluorophenyl)sulfonyl]1,3-thiazol-4-ylcarbamate (Preparation 4, 2.07 g, 5.04 mmol) was added and the reaction mixture stirred at ambient temperature. After 18 hours, the reaction mixture was diluted with water, neutralized with saturated aqueous ammonium chloride, and extracted with ethyl acetate (×3). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated onto diatomaceous earth. The residue was purified by automated silica gel flash chromatography (hexanes to ethyl acetate gradient elution) to afford tert-butyl({5-chloro-2-fluoro-4-[4-fluoro-2-pyridazin-4-yl-5-(trifluoromethyl)phenoxy]phenyl}sulfonyl)1,3-thiazol-4-ylcarbamate (1.75 g).

Provenance & Evidence