Step 2. Synthesis of ethyl 5-chloro-2-methylnicotinate: Under nitrogen protection, a mixture of ethyl 2,5-dichloronicotinate (10 g, 0.045 mol), tetrakis(triphenylphosphine)palladium (5.2 g, 4.5 mmol), trimethylcycloboroxane (5.65 g, 0.045 mol), and potassium carbonate (18.66 g, 0.16 mol) was dissolved in 1,4- dioxane (containing 10% water, 100 ml) and the reaction was refluxed for 7 hours. After completion of the reaction, the mixture was cooled to room temperature, poured into water and the aqueous phase was extracted with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by fast column chromatography on silica gel with hexane/ethyl acetate (50/1 to 20/1) as eluent to give 3.41 g of ethyl 5-chloro-2-methylnicotinate in 38% yield. The product was characterized by 1H-NMR (CDCl3): δ 8.57 (1H, d, J = 2.5 Hz), 8.17 (1H, d, J = 2.5 Hz), 4.39 (2H, dd, J = 7.1, 14.2 Hz), 2.81 (3H, s), 1.41 (3H, t, J = 7.1 Hz).
