[Synthesis]
General procedure for the synthesis of methyl 4-fluoro-3-methylbenzoate from methyl 4-bromo-3-methylbenzoate: methyl 4-bromo-3-methylbenzoate (27.5 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, 1.5 eq.), and toluene (2 mL) were added sequentially to an oven-dried, resealable screw-cap test tube equipped with a stir bar. After sealing the test tubes, they were removed from the glove box, wrapped in aluminum foil, and placed in a preheated 130°C oil bath with sufficient stirring for 18 hours of reaction. Upon completion of the reaction, the test tubes were removed from the oil bath and cooled to room temperature. P-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 plug to remove solid impurities. Subsequently, the clarified yellow solution was analyzed by 19F NMR (282 MHz) to determine the yield, and the conversion and reduction products were analyzed by GC. Yield was determined by comparing the 19F NMR integrals of p-fluorotoluene (-118 ppm) and methyl 4-fluoro-3-methylbenzoate (-106 ppm, 0.100 mmol, 83% yield).GC/MS analysis confirmed that the only compound in solution was methyl 4-fluoro-3-methylbenzoate. |