Cesium carbonate → 3-chloro-2-[(1R)-2,2,2-trifluoro-1-methylethoxy]pyridine

Participants

Reaction Conditions

Reaction Steps

To a solution of 3-chloro-2-fluoropyridine (500 mg, 3.8 mmol) and (2R)-1,1,1-trifluoropropan-2-ol (75 wt % solution in TBME, 752 mg, 4.9 mmol) in DMSO (7 mL) was added Cs2CO3 (1.6 g, 4.9 mmol) at room temperature under N2. The resulting mixture was stirred at 80° C. for 2 hours. To the reaction mixture was added another 500 mg of (2R)-1,1,1-trifluoropropan-2-ol and the mixture stirred at the same temperature for another 2.5 hours. The reaction mixture was cooled to room temperature, and partitioned between water and EtOAc. The organic phase was separated, washed with brine (2×30 mL), dried over Na2SO4, filtered, and concentrated in vacuo to give a crude product as colourless oil. The crude product was purified by silica gel column chromatography eluting with 0-30% EtOAc in heptane to give the title compound (365 mg, 43%) as colourless oil.

Provenance & Evidence