Synthesis
General procedure for the synthesis of 3-bromo-2,6-dimethylaniline from 1-bromo-2,4-dimethyl-3-nitrobenzene: 1-bromo-2,4-dimethyl-3-nitrobenzene (2.66 g, 11.6 mmol) was dissolved in acetic acid (48 mL) under stirring conditions, followed by the addition of iron powder (2.58 g, 46.3 mmol). The reaction mixture was heated at 80 °C for 18 hours. After completion of the reaction, it was cooled to room temperature and filtered. The filtrate was concentrated to dryness under reduced pressure and the resulting residue was alkalized with aqueous sodium hydroxide and then extracted three times with ethyl acetate. The organic phases were combined and dried with anhydrous magnesium sulfate. The dried organic phase was concentrated to dryness under reduced pressure. The crude product was purified by fast column chromatography using a gradient elution of 0-30% ethyl acetate in hexane to afford the target product 3-bromo-2,6-dimethylaniline (1.28 g, 6.40 mmol, 55.3% yield).
References
[1] Journal of Medicinal Chemistry, 2018, vol. 61, # 16, p. 7202 - 7217
[2] Patent: WO2015/79251, 2015, A1. Location in patent: Paragraph 00215
[3] Patent: KR2015/124677, 2015, A. Location in patent: Paragraph 0334; 0339-0342
[4] Patent: WO2009/44311, 2009, A1. Location in patent: Page/Page column 39
