Preparation of ethyl 6-hydroxynicotinate: to a solution of 6-hydroxynicotinate (5.0 g, 35.9 mmol) in anhydrous ethanol (180 mL) was slowly added concentrated sulfuric acid (1.0 mL). The reaction mixture was stirred at 60 °C for 20 min, followed by the addition of additional ethanol (33.0 mL), and the reaction system was heated to reflux with continuous stirring for 6.5 h. The reaction mixture was then stirred for 6.5 h at 60 °C for 1.5 min. Upon completion of the reaction, the reaction solution was cooled to 0 °C and saturated aqueous sodium bicarbonate solution was slowly added to neutralize the reaction solution. Subsequently, the ethanol was removed by concentration under reduced pressure by rotary evaporator. The aqueous phase was extracted with ethyl acetate and the organic phases were combined, washed with saturated brine and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure to give the white crystalline product ethyl 6-hydroxynicotinate (5.33 g, 89% yield). The product was characterized by 1H-NMR (CDCl3): δ 1.36 (3H, t, J = 7.1 Hz), 4.33 (2H, q, J = 7.1 Hz), 6.58 (1H, d, J = 9.5 Hz), 8.01 (1H, dd, J = 2.4, 9.5 Hz), 8.19 (1H, d, J = 2.4 Hz), 12.43 (1H brs).
