ethyl 2.4-dioxo-4-p-tolylbutanoate

Synthesis

(1) In a 250-mL three-necked flask, 24 g (0.348 mol) of sodium ethoxide and 200 mL of anhydrous toluene were added and mixed with stirring. Subsequently, 45.6 g (0.34 mol) of 4'-methylacetophenone was added slowly and dropwise over a period of 30 minutes to ensure uniform mixing. Next, 51.0 g (0.348 mol) of diethyl oxalate was added. After dropwise addition, the reaction mixture was heated to 50-60°C and stirred continuously for 4 hours. Upon completion of the reaction, it was cooled to room temperature, washed with 5% dilute hydrochloric acid solution and the pH was adjusted to the appropriate value. Liquid-liquid separation was carried out and the toluene layer was collected and dried with anhydrous sodium sulfate for 30 minutes. After filtration, the filtrate was distilled under reduced pressure to recover toluene. The residue was recrystallized from 95% ethanol to give 73.3 g of Intermediate 1 (purity: 99.1%) in 92% yield.

References

[1] Patent: CN108148003, 2018, A. Location in patent: Paragraph 0144; 0145; 0150; 0151; 0156; 0157; 0162; 0163
[2] Synthetic Communications, 2013, vol. 43, # 1, p. 110 - 117
[3] European Journal of Medicinal Chemistry, 2010, vol. 45, # 11, p. 4720 - 4725
[4] Organic and Biomolecular Chemistry, 2009, vol. 7, # 20, p. 4248 - 4251
[5] Annales de Chimie (Cachan, France), 1938, vol. <11> 9, p. 447,491