Water → Ethyl chloronicotinate

Participants

Reaction Steps

To a solution of 2-chloronicotinic acid (5 g, 31.7 mmol, Aldrich) in dimethylformamide (50 mL) were added potassium carbonate (6.579 g, 47.6 mmol) and ethyl iodide (3.8 mL, 47.7 mmol), respectively. The reaction mixture was stirred at room temperature for 3 d. Water (˜50 mL) was added and the product was extracted with ethyl ether (2×75 mL). The combined organic phases were washed with brine (1×50 mL), dried over anhydrous magnesium sulfate. The solids were filtered off, and the filtrate was concentrated under reduced pressure to give 2-chloronicotinic acid ethyl ester as yellow oil. It was then dissolved in ethanol (50 mL) and sodium ethoxide (17.8 mL, 47.6 mmol, 21% in ethanol, Aldrich) was added dropwise. Precipitation was seen as sodium ethoxide was added. The reaction mixture was stirred at room temperature for 12 h. The reaction mixture was concentrated and the residue partitioned between methylene chloride (150 mL) and water (50 mL). The aqueous layer was extracted with methylene chloride (1×50 mL). The combined organic layers were washed with brine (1×20 mL) and dried over anhydrous magnesium sulfate. The solids were filtered off, and the filtrate was concentrated in vacuo. The residue was purified by flash chromatography (120 g of silica gel, 10-30% ethyl acetate in hexane) to give 2-ethoxynicotinic acid ethyl ester as an orange oil (4.04 g, 65% yield for 2 steps).

Provenance & Evidence