Ethyl 3-(4-fluorophenyl)-3-oxopropanoate

Chemical Properties

Colorless liquid

Uses

Reactant used as a precursor in:

• Condensation reactions with diamines via C-C bond cleavage for synthesis of benzimidazoles and perimidines for possible use as antimalarial treatments
• Base-promoted domino Michael addition / cyclization / elimination reactions for synthesis of hydroxybenzophenones
• Oxidative cross-coupling with indoles via dioxygen activation
• Cyclization of keto esters for synthesis of pyrones
• Lewis base catalyzed hydrosilylation for synthesis of α-acetoxy β-amino acid derivatives
• Conia-ene reactions for synthesis of methylenecyclopentane derivatives

General Description

Ethyl (4-fluorobenzoyl)acetate on condensation with benzofurazan oxide yields 2-(carboethoxy)-3-(4′-fluoro)phenylquinoxaline1,4-dioxide.

Synthesis

403-42-9

105-58-8

1999-00-4

(Step 1) Diethyl carbonate (47.4 mL, 391 mmol) and sodium hydride (55 wt% paraffin oil dispersion, 23.7 g, 543 mmol) were sequentially added to a suspension of tetrahydrofuran (THF) at 60 °C, followed by slow addition of 4'-fluoroacetophenone (26.4 mL, 271 mmol). The reaction mixture was heated to reflux for 1 h. After cooling to room temperature, it was slowly poured into a mixture of acetic acid (33.6 mL, 586 mmol) and ice water (1 L). The reaction mixture was extracted with ether (2×500 mL), and the organic layer was washed with saturated aqueous sodium bicarbonate and saturated brine sequentially, dried over anhydrous sodium sulfate, and then the solvent was concentrated under reduced pressure to afford ethyl 3-(4-fluorophenyl)-3-oxopropanoate as a yellow oil (45.7 g, 100% yield, ketone formula: enol formula = 5:1). The product was characterized by 1H-NMR (400 MHz, CDCl3): keto formula: δ 1.26 (3H, t, J=7.2 Hz), 3.97 (3H, s), 4.22 (2H, q, J=7.2 Hz), 7.13-7.19 (2H, m), 7.96-8.01 (2H, m); enol formula: δ 1.34 (0.6H, t, J =7.2 Hz), 4.27 (0.4H, q, J=7.2 Hz), 5.61 (0.2H, s), 7.08-7.12 (0.4H, m), 7.76-7.80 (0.4H, m), 12.62 (0.2H, s).

References

[1] Molecules, 2004, vol. 9, # 3, p. 135 - 157
[2] Patent: EP2738170, 2014, A1. Location in patent: Paragraph 0465
[3] Tetrahedron Letters, 2014, vol. 55, # 14, p. 2212 - 2216
[4] Patent: US2014/213571, 2014, A1. Location in patent: Paragraph 0780
[5] Patent: EP1362846, 2003, A1. Location in patent: Page/Page column 41