Ethyl Glycolate → Ethyl 2-((5-bromo-3-nitropyridin-2-yl)oxy)acetate

Participants

Reaction Steps

To a suspension of sodium hydride (5.31 g, 133 mmol) in 1,4-dioxane (250 mL) was added drop wise ethyl glycolate (12.56 ml, 133 mmol) over a period of 30 minutes ensuring that the temperature was maintained below 30° C. The resulting thick suspension was stirred at room temperature for 15 minutes. In a separate 1 L round-bottomed flask was added 5-bromo-2-chloro-3-nitropyridine (21 g, 88 mmol) in 1,4-dioxane (150 mL) to give a brown solution. The sodium hydride/ethyl glycolate slurry was added drop wise over a period of 30 minutes. The resulting reaction mixture was heated to 80° C. overnight. The reaction mixture was concentrated under reduced pressure and the residue was purified via Biotage chromatography (silica 340 g column, gradient elution from 0% to 10% ethyl acetate in cyclohexane) to give a pale yellow solid (11.8 g, 43% yield). 1H NMR (500 MHz, CDCl3): 8.48 (1H, d), 8.42 (1H, d), 5.07 (2H, s), 4.25 (2H, q), 1.30 (3H, s).

Provenance & Evidence