Cesium carbonate → 2-Cyclopropyl-3-fluoro-5-nitroaniline

Temperatur

100 °C

A mixture of 2-bromo-3-fluoro-5-nitroaniline (1.6 g, 6.81 mmol, 1 equiv), cyclopropylboronic acid MIDA ester (Aldrich; 4.0 g, 20.43 mmol, 3 equiv), Pd(OAc)2 (238 mg, 1.06 mmol, 0.15 equiv), Cy3P (578 mg, 2.06 mmol, 0.3 equiv) and Cs2CO3 (13.26 g, 40.8 mmol, 6 equiv) in toluene (70 mL) and H2O (14 mL) was de-gassed with N2 for 5 minutes. The mixture was then heated at 100° C. (oil bath temperature) overnight. After allowing to cool to room temperature, the mixture was diluted with EtOAc (100 mL) and H2O (50 mL) and the mixture filtered through Celite. The filter cake was washed with EtOAc (2×50 mL) and the filtrate partitioned. The organic layer was evaporated under vacuum to leave a crude residue which was purified by column chromatography on silica gel using EtOAc/hexanes (1:4) as eluent to give the product (1.2 g, 90%) as a dark yellow solid.

1. customwas de-gassed with N2 for 5 minutes
2. temperatureto cool to room temperature
3. additionthe mixture was diluted with EtOAc (100 mL) and H2O (50 mL)
4. filtrationthe mixture filtered through Celite
5. washThe filter cake was washed with EtOAc (2×50 mL)
6. customthe filtrate partitioned
7. customThe organic layer was evaporated under vacuum
8. customto leave a crude residue which
9. customwas purified by column chromatography on silica gel

ORD-Eintrag

ord-e929fd94b6cd4f05be589ba0d3fc485c

Quelldatensatz

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09181222B2