Ammonia → 4-(1-Aminoethyl)-2-bromo-6-chloro-3-ethoxybenzonitrile

Temperature

60 °C

Titanium tetraisopropoxide (0.82 mL, 2.8 mmol) was added to a mixture of 4-acetyl-2-bromo-6-chloro-3-ethoxybenzonitrile (0.70 g, 2.3 mmol) and 2.0 M ammonia in ethanol (5.78 mL) at 0° C. The reaction was heated and stirred at 60° C. under nitrogen for 3 hours. The reaction was allowed to cool to room temperature, cooled in an ice bath and sodium tetrahydroborate (0.131 g, 3.47 mmol) was added, the solution was stirred at room temperature for another 2 hours. The reaction mixture was quenched with 2 M ammonia in water, and was stirred to allow a precipitate to form. The slurry was filtered and the solid was washed with EtOAc. The organic solvent was removed under vacuum and the residue was dissolved in methylene chloride. The organic layer was then washed with sat'd NaHCO3, water, brine, dried over MgSO4, filtered and concentrated to give 4-(1-aminoethyl)-2-bromo-6-chloro-3-ethoxybenzonitrile as an oil (0.7 g, 100%). The crude was used in the next step without purification. LCMS calculated for C11H13BrClN2O (M+H)+: m/z=302.9, 304.9. found: 302.9, 304.9.

1. temperatureThe reaction was heated
2. temperatureto cool to room temperature
3. temperaturecooled in an ice bath
4. stirringthe solution was stirred at room temperature for another 2 hours
5. customThe reaction mixture was quenched with 2 M ammonia in water
6. stirringwas stirred
7. customto form
8. filtrationThe slurry was filtered
9. washthe solid was washed with EtOAc
10. customThe organic solvent was removed under vacuum
11. dissolutionthe residue was dissolved in methylene chloride
12. washThe organic layer was then washed with sat'd NaHCO3, water, brine
13. dry with materialdried over MgSO4
14. filtrationfiltered
15. concentrationconcentrated

ORD record

ord-d167bf382ddb4620a2bae5999b15e9b5

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09096600B2