General procedure for the synthesis of ethyl 2-chloro-5-methylnicotinate from ethanol and 2-chloro-5-methylnicotinic acid: to a solution of 2-chloro-5-methylnicotinic acid (3.90 g, 22.7 mmol) in dichloromethane (DCM, 100 mL) was added oxaloyl chloride (9.95 mL, 114 mmol) followed by 1 drop of N,N-dimethylformamide (DMF). The reaction mixture was stirred at room temperature for 30 min, followed by evaporation of the solvent under vacuum. The resulting residue was dissolved in ethanol (EtOH, 66 mL) and stirring was continued for 2 h, after which the solvent was again evaporated under vacuum. The crude product was purified by fast column chromatography (silica gel SiO2, 120 g, eluent was a gradient solution of 0-50% dichloromethane in isohexane) to afford the target compound ethyl 2-chloro-5-methylnicotinate as a colorless oil (3.71 g, 82% yield).1H NMR (δ): 1.32 (3H, t), 2.34 (3H, s), 4.34 (2H , q), 8.06-8.07 (1H, m), 8.41-8.43 (1H, m). [Ref: Yamamoto S. et al, Bioorg. Med. Chem. 2012, 20, 422-434.]
