Cesium carbonate → 4-Cyclopropyl-3,5-difluoroaniline

Temperatur

100 °C

To a pressure tube was added 4-bromo-3,5-difluoroaniline (1.0 g, 4.8 mmol), cesium carbonate (4.7 g, 14.4 mmol), toluene (10 mL) and water (1 mL). The solution was de-gassed with N2 gas for 30 minutes, followed by the addition of cyclopropyltrifluoro-borate, potassium salt (0.8 g, 5.3 mmol), di(1-adamantyl)-n-butylphosphine hydroiodide (0.07 g, 0.14 mmol) and palladium(II) acetate (0.02 g, 0.096 mmol). De-gassing was continued for 5 minutes, the tube was sealed and heated at 100° C. for 18 hours. The cooled solution was diluted with EtOAc, washed with H2O and brine, dried (Na2SO4), and filtered. The filtrate was treated with 3-mercaptopropyl silica gel for 1 hour. The mixture was filtered and concentrated to give crude product which was purified by flash chromatography (0-30% EtOAc/hexane) to give the title compound (0.67 g, 4.0 mmol, 82%).

1. customThe solution was de-gassed with N2 gas for 30 minutes
2. customDe-gassing
3. customthe tube was sealed
4. additionThe cooled solution was diluted with EtOAc
5. washwashed with H2O and brine
6. dry with materialdried (Na2SO4)
7. filtrationfiltered
8. additionThe filtrate was treated with 3-mercaptopropyl silica gel for 1 hour
9. filtrationThe mixture was filtered
10. concentrationconcentrated
11. customto give crude product which
12. customwas purified by flash chromatography (0-30% EtOAc/hexane)

ORD-Eintrag

ord-9e4d9da843e449fe9bdd8ae3aa784ffa

Quelldatensatz

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08921514B2