反应详情

温度

0 °C

Dissolve tert-butyl N-(2-fluoro-4-hydroxy-phenyl)carbamate (10.47 g, 46.1 mmol) in N-methyl-2-pyrrolidone (NMP, 100 mL), add t-BuOK (5.67 g, 50.5 mmol) and stir at 0° C. for 30 min. Add 2-chloro-4-fluoropyridine (5.5 g, 41.9 mmol), then stir at 70° C. under N2 for 12 hrs. Quench the reaction with water, extract with EtOAc (300 mL×3), combine the organic layers, wash with brine (300 mL×2), dry over anhydrous Na2SO4. Concentrate under reduced pressure to give the crude product. Purification by chromatography (silica gel, EtOAc:PE=1:4) affords the title compound (11.23 g, 79.5%). MS: (M+1): 339.

1. customQuench
2. customthe reaction with water
3. extractionextract with EtOAc (300 mL×3)
4. washwash with brine (300 mL×2)
5. dry with materialdry over anhydrous Na2SO4
6. concentrationConcentrate under reduced pressure
7. customto give the crude product
8. customPurification by chromatography (silica gel, EtOAc:PE=1:4)