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

Temperature

60 °C

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.

1. additionThe addition
2. custom(˜40° C.)
3. extractionextracted into DCM (3×5 mL)
4. filtrationthe mixture was filtered through a phase separation cartridge
5. washThe combined organic phases were washed with brine (3 mL)
6. filtrationfiltered through another phase separation cartridge
7. dry with materialThe filtrate was dried by N2 blowing
8. customto give a crude product that
9. customwas purified by silica gel column chromatography
10. washeluting with 0-30% EtOAc in heptane

ORD record

ord-482d425cc0ff4a3ab75011e245816d70

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08592629B2