Uses
5-Methoxy-pyridine-3-carboxaldehyde is mainly used as an organic synthesis intermediate and can be used to synthesize various organic molecules containing a pyridine skeleton. Its highly reactive aldehyde group makes it an important starting material for synthesizing complex molecules.
Chemical Properties
White to yellow to orange to brown solid
Synthesis
3-Bromo-5-methoxypyridine (100 mg, 0.53 mmol) was placed in an oven-dried round-bottomed flask equipped with a magnetic stir bar and dissolved in anhydrous tetrahydrofuran (1 mL). Subsequently, isopropylmagnesium chloride (0.3 mL) was added at 0 °C and the resulting mixture was stirred at room temperature for 2 h (the solution turned light brown). Then, anhydrous tetrahydrofuran (0.1 mL) solution of N,N-dimethylformamide (0.1 mL) was slowly added. The initially formed solid gradually dissolved and the color of the solution changed from light brown to light yellow. after 1 h, the reaction mixture was cooled to 0 °C and the reaction was quenched with deionized water (2 mL). The organic layer was separated and the aqueous layer was further extracted with dichloromethane (3 x 3 mL). The organic layers were combined and dried over anhydrous sodium sulfate and subsequently concentrated in vacuum on a rotary evaporator. The crude product was purified by gradient silica gel column chromatography with the eluent being a solvent mixture of hexane and ethyl acetate (ratio from 20:1 to 1:1) to afford the target product 5-methoxy-pyridine-3-carbaldehyde as a colorless slurry (45 mg, 63% yield).1H NMR (500 MHz, CDCl3): δ 10.09 (s, 1H), 8.65 (d, J = 0.9 Hz, 1H), 8.54 (d, J = 3.1 Hz, 1H), 7.60 (dd, J = 5.1, 1.5 Hz, 1H).13C NMR (125 MHz, CDCl3): δ 190.6, 156.2, 145.1, 144.8, 132.0, 116.3, 55.7.
References
[1] Tetrahedron Letters, 2005, vol. 46, # 11, p. 1867 - 1871
[2] Tetrahedron, 2001, vol. 57, # 20, p. 4447 - 4454
[3] Biochemistry, 2010, vol. 49, # 49, p. 10421 - 10439
[4] Patent: US2014/309427, 2014, A1. Location in patent: Paragraph 0157; 0158
[5] Patent: WO2007/84560, 2007, A2. Location in patent: Page/Page column 164
