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

Uses

Reactant for:• ;Preparation of highly substituted furans by tandem condensation-cyclization reactions using bismuth triflate catalyst1• ;Co/Mn-mediated oxidative cross-coupling2• ;Enantioselective ruthenium-catalyzed hydrogenation3• ;Preparation of cambinol analogs for sirtuin inhibition with antitumor action4

Uses

Reactant for:

• Preparation of highly substituted furans by tandem condensation-cyclization reactions using bismuth triflate catalyst
• Co/Mn-mediated oxidative cross-coupling
• Enantioselective ruthenium-catalyzed hydrogenation
• Preparation of cambinol analogs for sirtuin inhibition with antitumor action

General Description

Ethyl (2-methylbenzoyl)acetate is a β-keto ester. It undergoes Co/Mn mediated oxidative coupling reaction with various indole derivatives.

Synthesis

577-16-2

105-58-8

51725-82-7

Diethyl carbonate (23.6 g, 200 mmol, 4.0 eq.) was slowly added to a stirred mixture of sodium hydride suspension (60% dispersed in mineral oil, 7.20 g, 180 mmol, 3.6 eq.) and toluene (300 mL) at room temperature. After stirring for 15 minutes, o-toluidine (6.70 g, 50.0 mmol, 1.0 eq.) was added and the reaction mixture was heated to reflux and maintained for 18 hours. Subsequently, glacial acetic acid (15 mL) was added dropwise over 10 minutes, followed by careful addition of ice water (150 mL). The mixture was extracted with ethyl acetate and the combined organic layers were dried over magnesium sulfate and subsequently concentrated under reduced pressure. The resulting residue was purified by silica gel fast column chromatography (elution gradient: 0 to 5% ethyl acetate in pentane solution) to afford 7.94 g (77% yield) of ethyl 3-oxo-3-(2-methylphenyl)propanoate as an oil (ketone/enol interconjugate isomer ratio 4:1).1H NMR (ketone interconjugate isomer) (400 MHz, CDCl3) δ: 7.66 (s 1H), 7.41 (s, 1H), 7.30-7.25 (m, 2H), 4.22-4.15 (m, 2H), 3.96-3.94 (m, 2H), 2.55 (s, 3H), 1.28-1.22 (m, 3H).

References

[1] Patent: US2012/22043, 2012, A1. Location in patent: Page/Page column 89
[2] Journal of Organic Chemistry, 2004, vol. 69, # 22, p. 7582 - 7591
[3] Patent: WO2015/183839, 2015, A1. Location in patent: Page/Page column 254; 255
[4] Chemistry - A European Journal, 2008, vol. 14, # 27, p. 8082 - 8085
[5] European Journal of Organic Chemistry, 2015, vol. 2015, # 17, p. 3656 - 3660