5-bromo-2-(2-methylpropyl)benzonitrile

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-amino-2-isobutylbenzonitrile (D57) (34 g) in acetonitrile (500 mL) was added HBr (24.37 mL) at 0° C. Then a solution of sodium nitrite (16.16 g) in water (50 mL) was added to the reaction mixture. After stirring for 30 min, copper(II) bromide (87 g) and copper(I) bromide (5.60 g) were added to the reaction mixture. The mixture was stirred at room temperature for 16 h. Saturated aqueous sodium bicarbonate solution was added to quench the reaction. The mixture was extracted with EA. The combined organic solution was dried over anhydrous sodium sulphate. After filtration and concentration, the residue was purified by column chromatography to give 5-bromo-2-(2-methylpropyl)benzonitrile (D58) (36 g) as a colorless oil. 6H (CDCl3, 400 MHz): 0.96 (6H, d), 1.98 (1H, m), 2.69 (2H, d), 7.18 (1H, d), 7.64 (1H, dd), 7.55 (1H, d). The mixture was stirred at room temperature for 16 h to quench the reaction The mixture was extracted with EA The combined organic solution was dried over anhydrous sodium sulphate After filtration and concentration the residue was purified by column chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5-Bromo-2-iodobenzonitrile (3.25 mmol) was combined with 6.5 mL of 0.5 M solution of iso-butylzinc bromide, the solution was degassed with argon, 100 mg of tetrakis(triphenylphosphine) palladium was added in one portion and the solution was stirred at rt under argon for 48 h. The solvents were removed under reduced pressure and the residual mixture was purified by column chromatography using Biotage 40L cartridge to obtain the title compound: 1H NMR (500 MHZ, CDCl3) δ 0.97 (d, J=8.5, 6H), 2.00 (m, 1H), 2.71 (d, J=7.5, 2H), 7.19 (d, J=8.5, 1H), 7.65 (dd, J=8.5, 2.0, 1H), 7.76 (d, J=2.0, 1H). the solution was degassed with argon, 100 mg of tetrakis(triphenylphosphine) palladium was added in one portion The solvents were removed under reduced pressure the residual mixture was purified by column chromatography