265652-38-8

81452-54-2

265652-38-8

Step 2: Synthesis of methyl 4-bromo-3-methylthiophene-2-carboxylate: Methyl 3-methylthiophene-2-carboxylate (20 g, 103 mmol, 1.0 eq.) and sodium hydroxide (12.3 g, 307 mmol, 3 eq.) were dissolved in acetic acid (75 mL) and heated to 60 °C. Bromine (46.9 g, 294 mmol, 2.85 eq.) was added slowly dropwise with controlled titration rate to maintain the temperature of the reaction mixture below 85 °C. The reaction mixture was stirred continuously at 85 °C for 6 hours. Subsequently, the solution was cooled to 50 °C and zinc powder (15.4 g, 236 mmol, 2.3 eq.) was added in batches, ensuring that the temperature did not exceed 85 °C after each addition. After addition, the mixture was continued to be stirred at 85 °C for 1 h. The mixture was then thermally filtered through a preheated bed of small diatomaceous earth. Water (300 mL) was added to the filtrate and extracted with hexane (300 mL). The organic phase was washed with water and concentrated to dryness to give 27 g (89% yield) of an off-white oil, which gradually crystallized after standing at room temperature. The product was characterized by 1H NMR (400 MHz, CDCl3): δ 7.43 (s, 1H), 3.87 (s, 3H), 2.56 (s, 3H).