19405-15-3Relevant academic research and scientific papers
Highly Chemo- And Enantioselective Hydrogenation of 2-Substituted-4-oxo-2-alkenoic Acids
Chen, Weiping,Jiang, Ru,Liu, Xian,Nie, Huifang,Wen, Jialin,Yao, Lin,Zhang, Xumu
supporting information, (2020/07/02)
The highly chemo- and enantioselective hydrogenation of (E)-2-substituted-4-oxo-2-alkenoic acids was established for the first time using the Rh/JosiPhos complex, affording a series of chiral α-substituted-γ-keto acids with excellent results (up to 99% yield and >99% ee) and high efficiency (up to 3000 TON). In addition, the importance of this methodology was further demonstrated by a concise and gram-scale synthesis of the anti-inflammatory drug (R)-flobufen.
A practical procedure for the synthesis of esonarimod, (R,S)-2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid, an antirheumatic agent (part 1).
Noguchi, Toshiya,Onodera, Akira,Tomisawa, Kazuyuki,Yokomori, Sadakazu
, p. 1407 - 1412 (2007/10/03)
An efficient and practical procedure for the synthesis of esonarimod, (R,S)-2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid (1), a new antirheumatic drug, has been developed. The intermediate, 2-methylene-4-(4-methylphenyl)-4-oxobutanoic acid (2), was prepared by Friedel-Crafts acylation of toluene with itaconic anhydride (3) in the presence of aluminum trichloride and nitrobenzene in 63% yield without silica gel column purification. Compound 1 was prepared by Michael addition of 2 with thioacetic acid (4) in 74% yield. Overall, 1 was obtained in 47% yield from 3. The structures and synthetic mechanisms of by-products (five compounds) of 2 were also clarified.
