Synthesis
To a stirred mixture of sodium hydride (3 mol eq.) and diethyl carbonate (4 mol eq.) in 50 mL of tetrahydrofuran (THF) washed with hexane (3 x 15 mL), p-methoxyacetophenone (1 mol eq.) was slowly added dropwise for a controlled period of 30 min or more. The reaction mixture was heated and refluxed for 3-4 h until the color of the reaction solution changed to dark brown and the reaction progress was monitored by thin layer chromatography (TLC, unfolding agent 10% ethyl acetate/hexane). Upon completion of the reaction, the mixture was cooled to room temperature and acidified with 5 mL of glacial acetic acid, followed by the addition of 100 mL of ice-cold dilute hydrochloric acid solution. The aqueous phase was extracted with ethyl acetate (3 x 75 mL) and the organic phases were combined and washed sequentially with saturated sodium bicarbonate solution, saturated saline and deionized water. The organic layer was dried with anhydrous sodium sulfate and concentrated under reduced pressure to give ethyl 3-(4-methoxyphenyl)-3-oxopropanoate as a viscous substance in good yield. The structure of the product was confirmed by 1H NMR and 13C NMR spectroscopy and the data were in agreement with literature reports.
References
[1] European Journal of Organic Chemistry, 2017, vol. 2017, # 31, p. 4543 - 4547
[2] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 14, p. 4237 - 4244
[3] Angewandte Chemie - International Edition, 2012, vol. 51, # 34, p. 8661 - 8664
[4] Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 17, p. 5064 - 5075
[5] European Journal of Organic Chemistry, 2012, # 35, p. 6976 - 6985
