反应详情

温度

90 °C

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.

1. customThe solvent was removed in vacuo and toluene (5 mL)
2. additionwas added
3. stirringstirred for 18 hours
4. temperatureThe reaction mixture was cooled to room temperature
5. additiondiluted with EtOAc and water
6. washThe organic phase was washed with saturated aqueous NaHCO3 solution
7. dry with materialbrine, dried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customto give the crude product as a dark brown oil
11. customThe crude product was purified by silica gel column chromatography
12. washeluting with 0-30% EtOAc in heptane