Trifluoroacetic acid → 3-Chloro-2-(3,3-difluorocyclobutyl)pyridine

Participants

Reaction Conditions

Reaction Steps

To a solution of tert-butyl 1-(3-chloropyridin-2-yl)-3,3-difluorocyclobutanecarboxylate (Preparation 229, 500 mg, 1.65 mmol) in DCM (6.5 mL) was added TFA (0.50 mL, 6.6 mmol) at room temperature under N2. The resulting solution was stirred for 18 hours. The solvent was removed in vacuo and toluene (5 mL) was added. The resulting mixture was warmed up to 90° C. and stirred for 18 hours. The reaction mixture was cooled to room temperature and diluted with EtOAc and water. The organic phase was washed with saturated aqueous NaHCO3 solution, then brine, dried over Na2SO4, filtered, and concentrated in vacuo to give the crude product as a dark brown oil. The crude product was purified by silica gel column chromatography eluting with 0-30% EtOAc in heptane to give the title compound (271 mg, 81%) as a colourless oil.

Provenance & Evidence