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

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence