Methyl iodide → 2-Chloro-4-fluoro-3-methylbenzonitrile

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To a solution of diisopropylamine (474 mL, 3.35 mol) in anhydrous THF (5.8 L) at −5° C. under a nitrogen atmosphere is added dropwise 2.5 M n-butyllithium in hexanes (1.24 L, 3.10 mol) over 3 h and the resulting mixture is stirred at −5° C. for one additional hour. The LDA solution is added dropwise to a solution of 2-chloro-4-fluoro-benzonitrile (400 g, 2.58 mol) in anhydrous THF (5.8 L) at −70° C. over 6 h and then stirred at −70° C. overnight. Iodomethane (643 mL, 10.32 mol) is added dropwise over 2.5 h and the temperature is raised to −5° C. for 17 h. Saturated aqueous ammonium chloride (3 L) is added. The solution is diluted with water (3.5 L) and extracted with diethyl ether (2×2 L). The organic phases are separated, combined, dried over anhydrous sodium sulfate, filtered, and concentrated to afford a black solid. The solid is purified through a silica gel pad eluting with EtOAc/hexanes (1/40) to obtain the title compound (323 g, 74%). 1H NMR (300 MHz, CDCl3) δ 7.08 (dd, J=8.6, 8.6 Hz, 1H), 7.54 (dd, J=8.6, 5.6 Hz, 1H), 2.36 (d, J=2.4 Hz, 3H).

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