Yield: 92%

Reaction Conditions:

with 3-chloro-benzenecarboperoxoic acid in dichloromethane for 24 h;Reflux;

Steps:

5 Preparation 5 2-Cyano-5-methylpyridine 1 -oxide
Add m-chloroperoxybenzoic acid (8.0 g, 46 mmol) in batches to a stirred solution of 5-methylpicolinonitrile (4.0 g, 34 mmol) in dichloromethane (60 mL). Stir the mixture under refluxing conditions for 24 hours and cool to room temperature. Wash the mixture with saturated Na₂S₂0₃ water solution (3 x 20 mL) and brine (3 x 20 mL), dry over Na₂S0₄ and concentrate under reduced pressure to give a residue. Purify the residue by silica gel flash chromatography, eluting with a gradient solvent of 50-100% ethyl acetate in petroleum ether to give the title compound as a yellow solid (4.2 g, 92%>). ES/MS (m/z) 135 (M+H).

References:

ELI LILLY AND COMPANY;LILLY CHINA RESEARCH AND DEVELOPMENT CO., LTD.;LIU, Kevin Kun-Chin;XIE, Yinong;WU, Liang;ZHOU, Guoqiang WO2015/89800, 2015, A1 Location in patent:Page/Page column 9