General procedure for the synthesis of ethyl 3-chloroisonicotinate from ethanol: 3-chloroisonicotinate (1.0 g, 6.35 mmol) was suspended in thionyl chloride (10 ml) and heated to reflux for 2.5 hours. Upon completion of the reaction, the solution was cooled to room temperature, concentrated to dryness and subsequently azeotropized with toluene (10 ml) to give an oil. The resulting oily substance was slowly added dropwise to a cooled mixture of ethanol (15 ml) and diisopropylethylamine (DIPEA) at 0°C, the dropwise process was controlled to be completed within 10 minutes. The reaction mixture was stirred at room temperature for 18 hours. At the end of the reaction, the reaction solution was concentrated in vacuum, diluted with water (20 ml) and extracted with ethyl acetate (30 ml). The organic phase was dried over anhydrous sodium sulfate and concentrated to give ethyl 3-chloroisonicotinate as an orange oil (1.1 g, 94% yield). The product was characterized by 1H NMR (CDCl3, 400MHz): δ 8.72 (s, 1H), 8.59 (d, J = 4.9Hz, 1H), 7.63 (dd, J = 4.9Hz, 0.5Hz, 1H), 4.44 (q, J = 7.3Hz, 2H), 1.42 (t, J = 7.3Hz, 3H).
