Methyl iodide → 1H-Pyrazole-4-carboxylic acid, 1-(2-hydroxyethyl)-5-methyl-, ethyl ester

Participants

Reaction Steps

Ethyl 1-(2-hydroxyethyl)-5-methyl-1H-pyrazole-4-carboxylate (376 mg, 67%) was synthesized from diethylaminomethylene ethyl acetoacetate (509 mg, 2.8 mmol) and 2-hydroxyethyl hydrazine (0.30 mL, 4.1 mmol) following the general procedure for ethyl 1-tert-butyl-5-methyl-1H-pyrazole-4-carboxylate as described (see R. A. Fecik, P. Devasthale, S. Pillai, A. Keschavarz-Shokri, L. Sehn, and L. A. Mitscher; J. Med. Chem. 2005, 48, 122). To a stirred solution of NaH (91 mg, 2.3 mmol) in THF (5 mL) was added ethyl 1-(2-hydroxyethyl)-5-methyl-1H-pyrazole-4-carboxylate (376 mg, 1.9 mmol) in THF (1 mL) at 0° C. followed by MeI (0.18 mL, 2.9 mmol). The resulting mixture was stirred for 15 h and quenched with saturated aqueous NH4Cl. The layers were separated and the aqueous layer was extracted with EtOAc (3×3 mL). The combined organic layer was dried over Na2SO4 and concentrated under reduce pressure. The residue was purified by column chromatography to provide ethyl 1-(2-methoxyethyl)-5-methyl-1H-pyrazole-4-carboxylate (249 mg, 62%) as a yellow oil.

Provenance & Evidence