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

Temperature

80 °C

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.

1. stirringthe mixture stirred at the same temperature for another 2.5 hours
2. temperatureThe reaction mixture was cooled to room temperature
3. custompartitioned between water and EtOAc
4. customThe organic phase was separated
5. washwashed with brine (2×30 mL)
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customto give a crude product as colourless oil
10. customThe crude product was purified by silica gel column chromatography
11. washeluting with 0-30% EtOAc in heptane

ORD record

ord-d9f9c76a300740808397182f3b6ed882

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08592629B2