125568-71-0

off-white powder

Under argon protection, 2,4-difluoro-5-nitrobenzoic acid (33.0 g, 162 mmol) was dissolved in 400 mL of anhydrous methanol, followed by the addition of 4 mL of concentrated sulfuric acid as a catalyst. The reaction mixture was heated to reflux for 15 hours. Upon completion of the reaction, the mixture was cooled to room temperature and subsequently concentrated under reduced pressure to remove the solvent. The concentrated residue was redissolved in 400 mL of ether and washed sequentially with saturated aqueous sodium bicarbonate (3 x 200 mL) and brine. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated to afford the target product methyl 2,4-difluoro-5-nitrobenzoate (32.6 g, 92% yield). The product was analyzed by APCI-MS showing a molecular ion peak m/z of 217.0, and analytical HPLC detection showed a retention time of 15.7 min and a purity greater than 99%.

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