Ammonium Chloride → 3-Amino-5-bromo-4-chlorobenzonitrile

(I1D): A mixture of 3-bromo-4-chloro-5-nitrobenzonitrile (0.99 g, 3.79 mmol), iron (1.057 g, 18.93 mmol) and ammonium chloride (2.025 g, 37.9 mmol) in THF, MeOH and water (60 ml, 1:1:1) was heated to reflux for 1 h. More iron (0.5 g) and NH4Cl (2 g) added, heated for another 2 h and then cooled to room temperature. Filtered off solid, the filtrate was concentrated to remove the organic solvent. The residue was diluted with water, extracted with EtOAc twice, dried and concentrated to dryness. The resulting solid was trituard with EtOAc, solid was filtered off through celite pad and the filtrate was concentrated to give 0.88 g of 3-amino-5-bromo-4-chlorobenzonitrile as yellow solid which was used as such in the next reaction. Intermediate 1: To a solution of 3-amino-5-bromo-4-chlorobenzonitrile (0.88 g, 3.80 mmol) in DCM (25 mL) was added TEA (1.590 mL, 11.41 mmol), BOC2O (1.059 mL, 4.56 mmol) and DMAP (0.464 g, 3.80 mmol). The mixture was stirred at room temperature for 16 h. The reaction mixture was concentrated, the crude product was purified using ISCO silica gel column (24 g, EtOAc/hexane=0-30%) to give 0.667 g of tert-butyl 3-bromo-2-chloro-5-cyanophenylcarbamate as white solid

1. temperaturewas heated
2. temperatureto reflux for 1 h
3. temperatureheated for another 2 h
4. filtrationFiltered off solid
5. concentrationthe filtrate was concentrated
6. customto remove the organic solvent
7. additionThe residue was diluted with water
8. extractionextracted with EtOAc twice
9. customdried
10. concentrationconcentrated to dryness
11. filtrationwas filtered off through celite pad
12. concentrationthe filtrate was concentrated

ORD-Eintrag

ord-64bcece14a95405682b0209f6ed95b9f

Quelldatensatz

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09273057B2