Synthesis
Example P3: Preparation of 2-bromo-6-chloro-3-nitropyridine. Under nitrogen protection, tert-butyl nitrite (990 mg, 9.60 mmol) was added batchwise to a stirred solution of 2-amino-6-chloro-3-nitropyridine (1.00 g, 5.76 mmol) and copper(II) bromide (1.56 g, 6.91 mmol) in acetonitrile (25 mL) at a reaction temperature of 65 °C. Stirring of the reaction mixture was continued for 30 minutes. After completion of the reaction, it was cooled to room temperature and the reaction mixture was partitioned between ethyl acetate and 2M aqueous hydrochloric acid solution. The organic layer was separated and dried with anhydrous magnesium sulfate and subsequently concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: heptane-dichloromethane gradient) to afford the target product 2-bromo-3-nitro-6-chloropyridine (1.11 g, 81% yield) as a yellow solid. Mass spectrometry (EI) analysis showed m/z of 235.9/237.9 (relative abundance 78/100, [M]+).
References
[1] Patent: US2007/185154, 2007, A1. Location in patent: Page/Page column 10
[2] Patent: US2015/57260, 2015, A1. Location in patent: Paragraph 0575; 0576
[3] Patent: WO2015/25026, 2015, A1. Location in patent: Page/Page column 142
[4] Journal of Medicinal Chemistry, 2017, vol. 60, # 24, p. 10151 - 10171
