Synthesis
General procedure: 2-chloro-5-fluoropyridine (20 g, 152 mmol) was dissolved in trifluoroacetic acid (150 mL) under nitrogen protection. Hydrogen peroxide (78 mL, 760 mmol) was slowly added to the solution at 70°C. The reaction mixture was stirred at 70°C for 16 hours. Upon completion of the reaction, the reaction solution was concentrated. Water and dichloromethane (DCM) were added to the residue. The pH was adjusted to 7 with 28% ammonium hydroxide solution and then extracted with DCM. The organic phase was dried with anhydrous magnesium sulfate (MgSO4) and concentrated to give 2-chloro-5-fluoropyridine 1-oxide (20.1 g, 136 mmol, 90% yield), and the product could be used in the next reaction without further purification.LC-MS analysis showed m/z 147.6 (M+H) with retention time of 0.78 min.
References
[1] Patent: WO2016/203401, 2016, A1. Location in patent: Page/Page column 191
[2] Patent: WO2011/113802, 2011, A2. Location in patent: Page/Page column 106
[3] Nucleosides, Nucleotides and Nucleic Acids, 2001, vol. 20, # 12, p. 1975 - 2000
[4] Patent: US2004/116362, 2004, A1. Location in patent: Page/Page column 12; Figure 1
[5] Patent: US2012/95031, 2012, A1. Location in patent: Page/Page column 158-159
