Sodium bis(trimethylsilyl)amide → 4-[(6-tert-butoxy-5-chloropyridin-3-yl)oxy]-5-chloro-2-fluoro-N-(methylsulfonyl)benzamide

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Reaction Steps

To a solution of tert-butyl 3,3-difluorocyclobutanecarboxylate (Preparation 227, 126 mg, 0.66 mmol) in toluene (2 mL) was added a solution of sodium 1,1,1,3,3,3-hexamethyldisilazan-2-ide (1M solution in THF, 1.6 mL, 1.6 mmol) at 0° C. The resulting solution was stirred for 10 minutes at the same temperature, then 5-chloro-4-[(5-chloro-6-fluoropyridin-3-yl)oxy]-2-fluoro-N-(methylsulfonyl)benzamide (Example 19, 200 mg, 0.50 mmol) was added. The resulting mixture was warmed up to room temperature and stirred for 36 hours. The reaction was quenched with saturated aqueous NH4Cl solution and extracted with EtOAc. The organic phase was washed with aqueous 1N citric acid solution, then brine, dried over Na2SO4, filtered, and concentrated in vacuo to give a crude product as a yellow oil. The crude product was purified by silica gel column chromatography eluting with 0-100% EtOAc in heptane to give a yellow foam. The foam was triturated with heptane to give the title compound (101 mg, 44%) as a white solid.

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