Water → HCID 12111908, compound

Participants

Reaction Steps

3-Acetyl-2,5-dichloro4-methylthiophene was prepared according the method of Eric C. Bigham, U.S. Pat. No. 4,110,342 (1978). To a stirred solution of 3-acetyl-2,5-dichloro-4-methylthiophene (593 mg, 2.84 mmol) in DME (15 mL) were added 4-pyridineboronic acid (0.87 g, 7.09 mmol), water (5 mL), sodium bicarbonate (1.76 g 20.9 mmol) and bis(triphenylphosphine)-palladium(II)chloride (0.2 g, 0.28 mmol) at room temperature under nitrogen. The mixture was heated at reflux temperature for 8 hours. After cooling, 4-pyridineboronic acid (0.3 g, 2.44 mmol), sodium bicarbonate (0.6 g, 7.14 mmol) and bis(triphenylphosphine)-palladium(II)chloride (0.1 g, 0.14 mmol) were added to the reaction mixture. The mixture was heated at reflux temperature for additional 3 hours. After cooling, the reaction mixture was filtered through celite pad. The filtrate was extracted with ethyl acetate (100 mL×2), and the combined organic layers were washed with brine, dried over MgSO4, and concentrated in vacuo. The resulting residue was purified by flash chromatography eluting with hexane-ethyl acetate (1:2) to provide the title product as a solid. Recrystallized from ethyl acetate gave the title product (468 mg, 56% yield).

Provenance & Evidence