1. 2-Acetyl-5-chlorothiophene (4.00 g, 24.8 mmol) was added in batches to fuming nitric acid (24 mL) cooled in an ice bath.
2. The reaction mixture was stirred at room temperature for 30 minutes and then poured into 200 mL of ice water.
3. The precipitated solid was extracted with ether, and the organic phase was dried, filtered, and concentrated in vacuum to afford the crude product 1-(5-chloro-4-nitrothiophen-2-yl)ethan-1-one (4.50 g, yellow solid), which did not require further purification.
4. 2,4-difluorothiophenol (4.30 g, 29.4 mmol) was added to a solution of sodium methanolate (1.40 g, 26.3 mmol) in methanol (250 mL).
5. The mixture was stirred at room temperature for 20 minutes before the crude product 1-(5-chloro-4-nitrothiophen-2-yl)ethan-1-one (5.50 g) was added.
6. The mixture was stirred overnight and then water (250 mL) was added, the solid formed was collected by filtration and dried under vacuum at 40 °C. The product was reconstituted by acetonitrile over a 2-minute period.
7. The product was recrystallized twice by acetonitrile to give 1-(5-((2,4-difluorophenyl)thio)-4-nitrothiophen-2-yl)ethanone (3.30 g, 39% yield) as a white solid.
8. 1H NMR (300 MHz, DMSO) δ 8.50, 8.00, 7.97, 7.95, 7.9, 7.71, 7.70, 7.68, 7.67, 7.65, 7.64, 7.43, 7.40, 7.37, 2.50.
