[Synthesis]
To a stirred solution of 2,6-dichloronicotinonitrile (0.50 g, 2.89 mmol) in methanol (10 mL) was added sodium methanolate (0.62 g, 2.89 mmol) at room temperature. The reaction mixture was heated to 60 °C and stirred continuously for 12 hours. Upon completion of the reaction, the mixture was cooled to room temperature and concentrated under reduced pressure. Subsequently, the reaction mixture was diluted with deionized water (40 mL) and extracted with ethyl acetate (2 x 75 mL). The organic layers were combined, washed with saturated saline (50 mL), dried over anhydrous sodium sulfate, and finally the solvent was evaporated under reduced pressure. The residue was purified by preparative high-performance liquid chromatography (HPLC) [using an Xbridge Phenyl column (21.2 × 250 mm ID, 5 μm); solvent A: 0.1% aqueous trifluoroacetic acid, solvent B: acetonitrile; gradient elution: 5-25% B, 25 min; flow rate: 20 mL/min] to afford 6-chloro-2-methoxy-3-pyridinecarbonitrile ( 0.48 g, 19% yield) as an off-white solid.1H NMR (400 MHz, CDCl3) δ ppm: 4.08 (s, 3H), 7.01-7.03 (d, J = 7.2 Hz, 1H), 7.80-7.82 (d, J = 8.0 Hz, 1H). lcms (method d): retention time 1.94 min, [M + H]+ m /z 169.2. |