(a) Synthesis of methyl 4-bromo-2,6-difluorobenzoate. At room temperature, (trimethylmethylsilyl) diazomethane (2.0 M ether solution, 15.0 mL, 30.0 mmol) was slowly added dropwise through a charging funnel to a mixture of dichloromethane (32.0 mL) and methanol (8.0 mL) of 4-bromo-2,6-difluorobenzoic acid (5.0 g, 21.10 mmol). The reaction mixture was stirred for 15 min and then concentrated under reduced pressure to afford methyl 4-bromo-2,6-difluorobenzoate (5.30 g, 21.11 mmol, 100% yield) as a clarified light orange oil. The product was characterized by 1H NMR (400 MHz, chloroform-d): δ 7.17 (dd, J = 8.8, 1.5 Hz, 2H), 3.95 (s, 3H). Mass spectrometry (ES+) analysis showed m/e 251/253 [M + H]+.
