Example 3.6: Preparation of methyl 4-bromo-2-methylbenzoate; Methyl 4-bromo-2-methylbenzoate (108 g, 471 mmol) was dissolved in N,N-dimethylformamide (4 L) under nitrogen protection followed by the addition of zinc(II) cyanide (88.5 g, 753.6 mmol) and tetrakis(triphenylphosphine)palladium(0) (65 g, 56.60 mmol). The reaction mixture was stirred at 100 °C for 16 hours. After completion of the reaction, the reaction mixture was diluted with toluene for phase separation. The aqueous phase was extracted twice with toluene. All organic phases were combined and washed sequentially with brine and saturated aqueous ammonium hydroxide solution, dried over anhydrous sodium sulfate and concentrated. The crude product was purified by silica gel column chromatography (eluent: ethyl acetate/cyclohexane, 1:5, v/v) to afford methyl 4-cyano-2-methylbenzoate (73 g, 89% yield).1H NMR (400 MHz, CDCl3): δ 7.78 (d, 1H), 7.52 (m, 2H), 3.92 (s, 3H), 2.62 (s, 3H).
