Synthesis
The general procedure for the synthesis of 4-bromo-2-iodo-1-methylbenzene from 2-amino-4-bromotoluene was as follows: intermediate 6 (4-bromo-2-iodo-1-methylbenzene) was synthesized in the scheme shown in Scheme 4, with the following experimental details. Step 1: 2-Methyl-5-bromoaniline (1.5 g, 8.06 mmol) was dissolved in diiodomethane (3.4 ml) at 0°C and tert-butyl nitrite (1.6 ml, 12.1 mmol) was slowly added. After removal of the ice bath, the reaction mixture was stirred at room temperature and subsequently heated at 80 °C for 30 min. Upon completion of the reaction, the solvent was removed by distillation under reduced pressure and the residue was purified by column chromatography (eluent: EtOAc/heptane) to afford the target compound 4-bromo-2-iodo-1-methylbenzene (1.6 g, 67% yield).LCMS analysis showed m/z 297 [M + H]+.1H NMR (300 MHz, CDCl3) δ: 7.96 (1H, s) 7.42-7.35 (1H, m), 7.12 (1H, d, J = 8.1 Hz), 2.40 (3H, s).
References
[1] Patent: US2011/39920, 2011, A1. Location in patent: Page/Page column 10
[2] Patent: WO2009/130434, 2009, A1. Location in patent: Page/Page column 21
[3] Patent: TW2016/9616, 2016, A. Location in patent: Paragraph 0161
