Synthesis
General procedure for the synthesis of 2-bromo-3-methoxy-6-nitropyridine from 2-bromo-3-methoxypyridine: 2-bromo-3-methoxypyridine (4.45 g, 23.7 mmol) was slowly added to a mixture of fuming nitric acid and concentrated sulfuric acid (1:1, v/v, total of 18 mL) that had been pre-cooled to 0 °C. The reaction mixture was kept stirred at 55 °C for 1.5 hours. Upon completion of the reaction, the mixture was carefully poured into ice water (150 mL) and a precipitate was immediately generated. The resulting precipitate was the target product 2-bromo-3-methoxy-6-nitropyridine, which could be used in the subsequent reaction without further purification. Yield: 3.54 g (64%) as a light yellow solid.1H NMR (DMSO-d6, 400 MHz) δ 8.41 (d, 1H), 7.80 (d, 1H), 4.06 (s, 3H).
References
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[4] Journal of Medicinal Chemistry, 1981, vol. 24, # 1, p. 39 - 42
[5] Patent: WO2007/51981, 2007, A1. Location in patent: Page/Page column 56
