Uses
Reactant involved in:• ;Synthesis of anticancer and antiviral agents1• ;Oxidation by organohypervalent iodine reagent2• ;Synthesis of monomers for preparation of functional polyesters3• ;Synthesis of calpain inhibitors4• ;Preparation of human A2A receptor antagonists5• ;Structural studies of dihydropteroate synthase inhibitors6
Definition
ChEBI: Diethyl 2-methyl-3-oxosuccinate is an alpha-ketoester, a beta-ketoester, an ethyl ester and a diester.
Synthesis
At room temperature, diethyl oxalate (300 g, 2.94 mol) and ethyl propionate (429.4 g, 2.94 mol) were dissolved in 1.8 L of anhydrous ethanol, followed by the addition of sodium ethoxide (300 g, 4.41 mol). The reaction mixture was stirred overnight. After completion of the reaction, the mixture was cooled to room temperature and the pH was adjusted to 7 with 6 N hydrochloric acid. subsequently, the mixture was concentrated under reduced pressure to remove the solvent. The concentrated residue was diluted with water and extracted with ethyl acetate. The organic layers were combined, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give diethyl oxalylpropionate (400 g, 67% yield) as a red liquid, which could be used in subsequent steps without further purification.1H NMR (400 MHz, CDCl3) δ ppm: 4.103-4.386 (m, 5H); 1.246-1.439 (m, 9H) .
References
[1] Journal of Medicinal Chemistry, 2013, vol. 56, # 23, p. 9701 - 9708
[2] Patent: US2015/25087, 2015, A1. Location in patent: Paragraph 0168; 0237; 0238
[3] Journal of the American Chemical Society, 1946, vol. 68, p. 132
[4] Justus Liebigs Annalen der Chemie, 1888, vol. 246, p. 329
[5] Journal of the Chemical Society, 1924, vol. 125, p. 313
