Synthesis
General procedure for the synthesis of 2-chloro-5-fluoro-3-nitropyridine from 2-hydroxy-3-nitro-5-fluoro-pyridine: 2-hydroxy-3-nitro-5-fluoro-pyridine (1.00 g, 5.33 mmol) was dissolved in acetonitrile (40 mL), followed by the addition of a solution of tetraethylammonium chloride (2.10 g, 12.65 mmol) in acetonitrile. After the mixture was clarified, phosphorus trichloride (1.94 g, 12.65 mmol) was added slowly and dropwise at room temperature. The reaction mixture was heated to 90°C and maintained for 24 hours. After completion of the reaction, the mixture was concentrated to dryness under reduced pressure. The residue was dissolved in water (100 mL) and extracted with ethyl acetate (2 x 100 mL). The organic layers were combined, dried with anhydrous sodium sulfate, filtered and concentrated to dryness under reduced pressure to give a yellow solid product (0.90 g, 69% yield), which was pure enough to be used directly in subsequent synthesis steps. Low resolution mass spectrometry (LRMS) showed m/z: 177 ([M+H]+).
References
[1] Patent: US2011/28467, 2011, A1. Location in patent: Page/Page column 52
[2] Patent: EP2518071, 2012, A1. Location in patent: Page/Page column 43
[3] Patent: WO2006/114706, 2006, A1. Location in patent: Page/Page column 45
[4] Journal of Heterocyclic Chemistry, 1996, vol. 33, # 2, p. 287 - 293
[5] Patent: US2004/110785, 2004, A1. Location in patent: Page 77
