The general procedure for the synthesis of ethyl 3-methylpyrazole-5-carboxylate from ethyl acetylpyruvate was as follows: hydrazine monohydrate (5.4 mL, 110.68 mmol) was slowly added dropwise to a solution of EtOH/AcOH (100/1 mL) of ethyl 2,4-dioxovalerate (11.67 g, 73.79 mmol) at 0 °C. The reaction mixture was stirred at room temperature for 15 h. The reaction mixture was poured into water (50 mL) and saturated aqueous NaHCO3 solution (5 mL) and extracted with EtOAc (3 x 50 mL). The organic layers were combined, dried with anhydrous Na2SO4, filtered and concentrated under reduced pressure to afford ethyl 5-methyl-1H-pyrazole-3-carboxylate (8.41 g, white solid, 74% yield), which could be used for the subsequent reaction without further purification. The product was characterized as follows: 1H NMR (CDCl3, 250 MHz): δ 6.55 (s, 1H), 4.34 (q, J = 7.13 Hz, 2H), 2.35 (s, 3H), 1.33 (t, J = 7.13 Hz, 3H); EI-MS: m/z = 155 [M+1]+.
