3-Chloro-2-fluoropyridine → 3-chloro-2-[(1S)-2,2,2-trifluoro-1-methylethoxy]pyridine

Participants

Reaction Conditions

Reaction Steps

To a solution of 3-chloro-2-fluoropyridine (115 mg, 0.88 mmol) and (25)-1,1,1-trifluoropropan-2-ol (45 wt % solution in TBME, 218 mg, 0.88 mmol) in THF (1 mL) was added potassium 2-methylpropan-2-olate (120 mg, 1.05 mmol) at room temperature under N2. The addition was slightly exothermic (˜40° C.). The resulting solution was warmed up to 60° C. for 10 minutes. The reaction mixture was diluted with water and extracted into DCM (3×5 mL) and the mixture was filtered through a phase separation cartridge. The combined organic phases were washed with brine (3 mL) and filtered through another phase separation cartridge. The filtrate was dried by N2 blowing to give a crude product that was purified by silica gel column chromatography eluting with 0-30% EtOAc in heptane to give the title compound (128 mg, 65%) as colourless oil.

Provenance & Evidence