Sodium bis(trimethylsilyl)amide → Tert-butyl 1-(3-chloropyridin-2-yl)-3,3-difluorocyclobutanecarboxylate

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Reaction Steps

A solution of 3-chloro-2-fluoropyridine (500 mg, 3.8 mmol) and tert-butyl 3,3-difluorocyclobutanecarboxylate (Preparation 227, 877 mg, 4.6 mmol) in toluene (13 mL) was cooled to 0° C. A solution of sodium 1,1,1,3,3,3-hexamethyldisilazan-2-ide (1M solution in THF, 5.7 mL, 5.7 mmol) was added dropwise. The reaction mixture was stirred for 20 minutes at the same temperature, and then allowed to warm to room temperature and stirred for 4 hours. The reaction was quenched with saturated aqueous NH4Cl solution and extracted with EtOAc (3×20 mL). The combined organic extracts were washed with 1N aqueous citric acid solution (3×15 mL), then brine (3×15 mL). The organic phase was dried over Na2SO4, filtered, and concentrated in vacuo to give a crude product as yellow oil which was purified by silica gel column chromatography eluting with 0-20% EtOAc in heptane to give the title compound (505 mg, 44%) as colourless oil.

Provenance & Evidence