The general procedure for the synthesis of 2-thiophenecarbonyltrifluoroacetone from 2-acetylthiophene and ethyl trifluoroacetate was as follows: 1-(thiophen-2-yl)ethanone (20 g, 16 mmol) was added dropwise to a methanolic solution of sodium methanolate (10.3 g, 19 mmol), and the reaction was stirred for 1 hour at room temperature. Subsequently, the reaction mixture was cooled to 0 °C, ethyl 2,2,2-trifluoroacetate (27 g, 19 mmol) was added in batches and the whole reaction mixture was refluxed at 80 °C overnight. Upon completion of the reaction, the organic solvent was removed by vacuum evaporation and the residue was dissolved in water (200 mL), acidified with 1N hydrochloric acid (120 mL) and subsequently extracted three times with ethyl acetate (200 mL). The organic layers were combined, washed with brine, dried over anhydrous sodium sulfate, concentrated and further purified by silica gel column chromatography (petroleum ether/ethyl acetate, 20:1) to afford 4,4,4-trifluoro-1-(thiophen-2-yl)butane-1,3-dione (11 g, 32% yield) as a light red solid.
