The general procedure for the synthesis of 3-methyl-4-fluorobenzonitrile from 4-bromo-3-methylbenzonitrile was as follows: to an oven-dried, sealable reaction tube fitted with a stirrer were added sequentially 4-bromo-3-methylbenzonitrile (23.3 mg, 0.12 mmol), BrettPhos (6.4 mg, 0.012 mmol, 10 mol%), (COD)Pd( CH2TMS)2 (2.3 mg, 0.006 mmol, 5 mol%), AgF (22.8 mg, 0.18 mmol) and toluene (2 mL). The reaction tubes were sealed and removed from the glove box, wrapped in aluminum foil and placed in a preheated 130°C oil bath with continuous stirring for 18 hours. Upon completion of the reaction, the reaction tube was removed from the oil bath and cooled to room temperature. 4-Fluorotoluene (6.5 μL, 0.06 mmol, 0.5 eq.) and dodecane (27.3 μL, 0.12 mmol, 1 eq.) were added as internal standards. The reaction mixture was filtered through a glass filter and Celite pad to remove solids. The resulting clarified light yellow solution was analyzed for product yield by 19F NMR (282 MHz) and for conversion and reduction products by GC.
