[Synthesis]
General procedure for the synthesis of ethyl 5-bromo-3-ethoxy-1H-pyrazole-4-carboxylate from ethyl 3-ethoxy-1H-pyrazole-4-carboxylate: Ethyl 3-ethoxy-1H-pyrazole-4-carboxylate (0.74 g, 4.02 mmol) and N-bromosuccinimide (0.75 g, 4.22 mmol) or N-iodosuccinimide (0.94 g, 4.22 mmol) were dissolved in cyclohexane (50 mL) and the reaction was refluxed for 30 minutes or 24 hours. After completion of the reaction, the resulting suspension was concentrated to dryness and purified by silica gel column chromatography (eluent: dichloromethane/ethanol, 98:2) to afford ethyl 5-bromo-3-ethoxy-1H-pyrazole-4-carboxylate (12a, 0.75 g, 60% yield) or ethyl 3-bromo-5-ethoxy-1H-pyrazole-4-carboxylate (12b, 0.5 g, 47% yield). 3-bromo Ethyl 5-ethoxy-1H-pyrazole-4-carboxylate (12b) was white crystals.1H NMR (CDCl3): δ 1.40 (t, 3H, J = 7.0 Hz), 1.48 (t, 3H, J = 7.0 Hz), 4.33 (m, 4H), 9.5 (s, 1H).13C NMR (CDCl3; only two broad signals): δ 14.2, 14.5, 60.4, 65.7, 99.0, 119.5 (br), 161.6 (br), 162.0. HRMS (ESI): m/z Calculated value of C8H11BrN2O3 + H [M + H]+: 263.0031, measured value: 263.0049. |