The general procedure for the synthesis of 5-[1-hydroxy-2-(2,4,5-trifluorophenyl)ethylidene]-2,2-dimethyl-1,3-dioxane-4,6-dione from cyclo(isopropylidene)malonate (Meldrum acid) and 2,4,5-trifluorophenylacetic acid is as follows: in a 1000 mL three-necked flask, sequentially add 2,4,5-trifluorophenylacetic acid (25 g , 0.132 mol), Meldrum acid (21 g, 0.145 mol) and 4-dimethylaminopyridine (DMAP, 1.29 g, 0.0011 mol). Acetonitrile (75 mL) was added as a solvent in a single addition at room temperature. Subsequently, N,N-diisopropylethylamine (49.2 mL, 0.283 mol) was added as a one-time addition while keeping the reaction temperature below 40 °C. Next, pivaloyl chloride (17.8 mL, 0.145 mol) was slowly added dropwise over a period of 1 to 2 hours and the temperature was controlled to not exceed 40 °C. After the dropwise addition, the reaction mixture was stirred at 45-50 °C for 2-3 hours and then cooled to 0 °C. Over a period of 1 hour, 1N HCl (300 mL) was added slowly and dropwise to induce crystallization of the Meldrum acid adduct. The product was collected by filtration and washed with 20% aqueous acetonitrile. After drying, 36.5 g of Meldrum acid adduct was obtained in 88% yield. The structure of the product was confirmed by 1H-NMR (400 MHz, CDCl3) and 13C-NMR (100 MHz, CDCl3).
