Synthesis
To a 500 mL single-necked flask was added 200 mL of a solvent mixture of acetonitrile-isopropanol (1:1, v/v), 200 mmol (26.8 mL) of 4'-methylacetophenone (I) and 600 mmol (72 mL) of trifluoroacetic acid ethyl ester (II) were added sequentially, followed by the addition of 360 mmol of potassium carbonate with a particle size of 600 nm. The reaction mixture was stirred at 40°C for 24 hours. Upon completion of the reaction, the potassium carbonate was recovered by filtration along with the by-product potassium bicarbonate, which could be regenerated and used after high temperature treatment. The filtrate was distilled under reduced pressure to recover the solvent and unreacted raw materials for subsequent use. To the distillation residue, an equal volume of water was added and the pH was adjusted to 6 with 10% hydrochloric acid solution, followed by extraction with ethyl acetate (70 mL each time) for four times. The organic phases were combined, concentrated and freeze-crystallized to give a light yellow solid product, 4,4,4-trifluoro-1-(4-methylphenyl)-1,3-butanedione (III) 45.6 g in 99.08% yield.
References
[1] Patent: CN103951549, 2016, B. Location in patent: Paragraph 0008; 0027-0028
[2] Patent: CN107759519, 2018, A. Location in patent: Paragraph 0033-0035
[3] Journal of Medicinal Chemistry, 2007, vol. 50, # 18, p. 4444 - 4452
[4] Journal of Medicinal Chemistry, 1997, vol. 40, # 9, p. 1347 - 1365
[5] Patent: WO2005/49014, 2005, A1. Location in patent: Page/Page column 137
