11A: Synthesis of methyl 4-bromo-3-methylbenzoate
Zinc cyanide (6.2 g, 52 mmol) and tetrakis(triphenylphosphine)palladium(0) (4 g, 3 mmol) were added to a solution of methyl 4-bromo-3-methylbenzoate (20 g, 87 mmol) in DMF (100 mL). The reaction mixture was stirred at 120 °C for 4 hours. After completion of the reaction, the mixture was cooled to room temperature, diluted with EtOAc (700 mL) and washed sequentially with water and brine. The organic layer was dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Purification by fast column chromatography (silica gel, eluent ratio 1:3 EtOAc:hexane) afforded methyl 4-cyano-3-methylbenzoate (12.3 g, 39.8% yield) as a white solid.1H NMR (400 MHz, CDCl3) δ 2.59 (s, 3H), 3.93 (s, 3H), 7.66 (d, J=8.0 Hz. 1H), 7.90 (d, J=8.0Hz, 1H), 7.97 (s, 1H).
