Synthesis
Step 1: (S)-1-(2,6-dichloro-3-fluorophenyl)ethanol (20.9 g, 0.10 mol) was dissolved in anhydrous tetrahydrofuran (200 mL) under nitrogen protection. Subsequently, 3-hydroxy-2-nitropyridine (16.0 g, 0.11 mol) and triphenylphosphine (40.0 g, 0.15 mol) were added sequentially and stirred at room temperature for 1 hour. The reaction system was cooled to 0 °C and diisopropyl azodicarboxylate (DIAD, 40 mL, 0.15 mol) was added slowly and the reaction continued to stir for 12 hours. After completion of the reaction, the solvent was removed by distillation under reduced pressure to obtain the crude product. Purification by silica gel column chromatography afforded the target product (R)-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-2-nitropyridine (20.2 g, 61% yield).
References
[1] Patent: US2006/46991, 2006, A1. Location in patent: Page/Page column 20
[2] Patent: WO2006/21886, 2006, A1. Location in patent: Page/Page column 51
[3] Organic Process Research and Development, 2011, vol. 15, # 5, p. 1018 - 1026
[4] Patent: CN105348265, 2016, A. Location in patent: Paragraph 0056; 0057; 0058
[5] Patent: CN103664896, 2016, B. Location in patent: Paragraph 0108; 0109
