5-Thiazolecarboxylic acid, 2-acetyl-, Methyl ester synthesis

Yield:1261080-59-4 80%

Reaction Conditions:

with tert.-butylhydroperoxide;ferrous(II) sulfate heptahydrate;sulfuric acid in water at 25;Minisci acetylation;

Steps:

1. Methyl-2-acetylthiazole-5-carboxylate (7)

A solution of FeSO₄·7H₂O (33.4 g, 120 mmol) in 80 ml H₂O and 70% tert-butyl hydroperoxide (12 ml, 120 mmol) were added to a stirred and cooled (10-20 ) mixture of the methyl-thiazole-5-carboxylate 6 (2.86 g, 20 mmol), 4 M H₂SO₄ (10 ml), and the 40% aldehyde (13.22 g, 120 mmol) separately and simultaneously. The reaction mixture was stirred at room temperature (25 ) for 1 h, extracted with EtOAc and washed with saturated Na₂S₂O₃ solution and brine. After drying over anhydrous Na₂SO₄ and removing the solvent, a crude material was obtained. The material was purified by column chromatography (PE:EtOAc, 50:1, v/v) to afford compound 7 (2.97 g, 80%) as pale yellow solid. MS (ESI) m/z 186.0 [M+H]⁺. ¹H NMR (400 Hz, CDCl₃) δ 8.50 (s, 1H), 3.95 (s, 3H), 2.73 (s, 3H) .

References:

Chang, Shaohua;Zhang, Zhang;Zhuang, Xiaoxi;Luo, Jinfeng;Cao, Xianwen;Li, Honglin;Tu, Zhengchao;Lu, Xiaoyun;Ren, Xiaomei;Ding, Ke [Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,# 2,p. 1208 - 1212] Location in patent:supporting information; experimental part