METHYL 5-HYDROXY-PYRAZOLE-3-CARBOXYLATE synthesis

Yield:1018446-60-0 80%

Reaction Conditions:

with hydrazine hydrate;acetic acid in toluene at 20; for 2 h;

Steps:

6.1.1.1. Methyl 3-hydroxy-1H-pyrazole-5-carboxylate (4)

To a solution of hydrazine monohydrate (44.8 g, 894 mmol) in toluene (300 mL) was added AcOH (180 mL) followed by addition of acetylenedicarboxylic acid dimethyl ester (100 mL, 813 mmol). After being stirred at room temperature for 2 h, the mixture was poured into ice-cooled water. The resulting precipitate was collected, washed with water and hexane, and dried to give 4 (92.2 g, 80%) as a white solid. 1H NMR (DMSO-d₆): δ 3.77 (s, 3H), 5.96 (br s, 1H), 10.04 (br s, 1H), 12.79 (br s, 1H).

References:

Rikimaru, Kentaro;Wakabayashi, Takeshi;Abe, Hidenori;Imoto, Hiroshi;Maekawa, Tsuyoshi;Ujikawa, Osamu;Murase, Katsuhito;Matsuo, Takanori;Matsumoto, Mitsuharu;Nomura, Chisako;Tsuge, Hiroko;Arimura, Naoto;Kawakami, Kazutoshi;Sakamoto, Junichi;Funami, Miyuki;Mol, Clifford D.;Snell, Gyorgy P.;Bragstad, Kenneth A.;Sang, Bi-Ching;Dougan, Douglas R.;Tanaka, Toshimasa;Katayama, Nozomi;Horiguchi, Yoshiaki;Momose, Yu [Bioorganic and Medicinal Chemistry,2012,vol. 20,# 2,p. 714 - 733] Location in patent:experimental part