O-Xylene → 4-Bromo-4-chloroaniline

Temperature

150 °C

A mixture of isopropyl [2,4-dichloro-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]acetate (Reference Example 10; 1.33 g, 3.72 mmol), 4-bromo-2-chloroaniline (1.92 g, 9.31 mmol), p-toluenesulfonic acid monohydrate (707.6 mg, 3.98 mmol) and xylene (10.0 mL) was stirred at 150° C. for 2 hr. After cooling, the reaction mixture was diluted with water and extracted with ethyl acetate (×3). The combined organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with a 0-15% ethyl acetate/n-hexane gradient mixture to give isopropyl {2-[(4-bromo-2-chlorophenyl)amino-4-chloro]-7-(1-ethylpropyl)-1H-benzimidazol-1-yl}acetate and 4-bromo-4-chloroaniline. The mixture was used for the next step without further purification.

1. temperatureAfter cooling
2. extractionextracted with ethyl acetate (×3)
3. washThe combined organic layer was washed with brine
4. dry with materialdried over anhydrous magnesium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe residue was purified by silica gel column chromatography
8. washeluting with a 0-15% ethyl acetate/n-hexane gradient mixture

ORD record

ord-5d6c962d6ca14c6d9dde30766e2954c0

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08785460B2