3-Oxo-3-m-tolyl-propionic acid ethyl ester

Uses

Reactant for:• ;Stereoselective ketonization-olefination of indoles by Co/Mn-mediated oxidative cross-coupling of indoles via dioxygen activation1• ;Enantioselective Michael reaction2• ;SEGPhos-ruthenium-catalyzed asymmetric hydrogenation3

Uses

Reactant for:

• Stereoselective ketonization-olefination of indoles by Co/Mn-mediated oxidative cross-coupling of indoles via dioxygen activation
• Enantioselective Michael reaction
• SEGPhos-ruthenium-catalyzed asymmetric hydrogenation

Synthesis

105-58-8

585-74-0

33166-79-9

GENERAL STEPS: In a dry reaction flask, sodium hydride (3.1 g, 77.1 mmol) was suspended in diethyl carbonate, followed by the slow addition of 3'-methylacetophenone (4.5 g, 33.54 mmol). The reaction mixture was heated at 80 °C and stirred continuously for 2 hours. Upon completion of the reaction, ice water and acetic acid were carefully added to the reaction mixture to quench the reaction. The resulting mixture was washed with saturated sodium chloride solution and then extracted with ethyl acetate. The organic layer was separated and dried with anhydrous magnesium sulfate and subsequently concentrated under reduced pressure. The resulting residue was purified by fast column chromatography to give 5.8 g of ethyl (3-methylbenzoyl)acetate in 84% yield. The product was characterized by 1H-NMR (200 MHz, CDCl3): δ 7.73-7.63 (m, 2H), 7.42-7.28 (m, 2H), 4.27-4.18 (m, 2H), 3.97 (s, 2H), 2.40 (s, 3H), 1.36-1.23 (m, 3H).

References

[1] Journal of Medicinal Chemistry, 2006, vol. 49, # 6, p. 1910 - 1915
[2] Patent: WO2005/100297, 2005, A1. Location in patent: Page/Page column 28-29
[3] Patent: WO2005/100303, 2005, A1. Location in patent: Page/Page column 56
[4] Chemical and Pharmaceutical Bulletin, 1982, vol. 30, # 7, p. 2590 - 2594
[5] Angewandte Chemie - International Edition, 2012, vol. 51, # 34, p. 8661 - 8664