General procedure for the synthesis of ethyl 4-methylthiazole-5-carboxylate from ethyl 2-amino-4-methylthiazole-5-carboxylate: compound 3a (4.0 g, 21.5 mmol) was dissolved in 106 mL of 30% hypophosphite (H3PO2) solution. The reaction system was cooled to -5°C, after which sodium nitrite (NaNO2, 3.0 g, 2.0 eq.) was dissolved in 12 mL of water and slowly added dropwise to the reaction solution. After the dropwise addition, the reaction mixture was transferred to 0°C and kept for 1 hour, then stirring was continued for 2 hours at room temperature. Subsequently, pre-cooled sodium hydroxide solution (17 g NaOH dissolved in 200 mL of water) was added slowly dropwise. The reaction mixture was adjusted to neutral with sodium bicarbonate (NaHCO3) solution and then extracted with ether (Et2O, 50 mL x 3). The organic phases were combined and purified by column chromatography (eluent ratio: petroleum ether:ethyl acetate = 50:1, v/v) to give the yellow semi-solid product 3b (2.1 g, 56% yield).
