Synthesis
3.16 General procedure for the synthesis of 1-methyl-1H-pyrazol-5-ol (25a): a solution of methylhydrazine (2b) (0.57 mL, 10.9 mmol) in toluene (PhMe) (2 mL) was slowly added dropwise to a solution of ethyl acetoacetate (24) (1.39 mL, 10.9 mmol) in toluene (PhMe) (3 mL). The reaction mixture was stirred at room temperature for 5 min before the solvent was removed by vacuum evaporation. The product was purified by recrystallization (methanol/ethyl acetate mixed solvent) to give 1,3-dimethyl-5-hydroxypyrazole (0.90 g, 74% yield) as a light yellow solid with a melting point of 112-115°C (literature value: 112.5-113.5°C) (measured value: 113.0709). Molecular formula C5H9N2O [MH] Calculated value: 113.0709; FTIR (KBr) νmax/cm-1: 1549, 1269, 1185, 1034; 1H NMR (400 MHz, CDCl3) δ: 3.21 (3H, s, Me), 3.11 (2H, s, CH2), 2.02 (3H, s, 3-Me ); 13C NMR (100 MHz, CDCl3) δ: 172.2 (C), 155.5 (C), 41.4 (CH2), 31.0 (Me), 16.9 (Me); LRMS (APcI) m/z (Relative Intensity): 113 (MH+, 100).
References
[1] Tetrahedron, 2013, vol. 69, # 39, p. 8429 - 8438
[2] Letters in Drug Design and Discovery, 2016, vol. 13, # 8, p. 800 - 808
[3] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 10, p. 2590 - 2594
