General procedure for the synthesis of 2-fluoro-6-bromobenzyl bromide from 2-fluoro-6-bromobenzenemethanol: To a chloroform (14L) solution of 2-fluoro-6-bromobenzenemethanol (1.61kg, 7.85mol) was added pyridine (770mL, 9.52mol) at 0°C. The reaction was slightly exothermic, and the reaction was stirred for 5 minutes. Subsequently, phosphorus tribromide (900 mL, 9.49 mol) was added dropwise while keeping the internal temperature below 20 °C. The reaction mixture was stirred overnight and allowed to warm up naturally to room temperature. Upon completion of the reaction, the mixture was cooled to 0 °C and quenched slowly with ice water (2 L). The reaction mixture was transferred to a 50L flask and layered. The aqueous layer was extracted with chloroform (1L). The organic phases were combined and washed sequentially with 5% sulfuric acid (2L), saturated aqueous sodium bicarbonate (2L) and brine (2L). The organic phase was dried with magnesium sulfate, filtered and concentrated to give 2-fluoro-6-bromobenzyl bromide as a yellow oil (1753 g, 83% yield).1H NMR (CDCl3) δ 7.43 (d, 1H), 7.21 (m, 1H), 7.09 (t, 1H), 4.68 (s, 2H).
