Methyl lithium (1.6 M ether solution, 16.4 mL, 26.3 mmol) was slowly added to a stirred solution of methyl 2-aminopyridine-4-carboxylate (35) (1.00 g, 6.57 mmol) in tetrahydrofuran (THF) (100 mL) at -78 °C and protected by nitrogen, and the addition time was controlled to be within 10 minutes. The reaction temperature was maintained at -78 °C with continued stirring for 30 min, after which the reaction mixture was slowly warmed up to 0 °C and the reaction continued for 3 hours. Upon completion of the reaction, isopropanol (8.0 mL) was carefully added at 0 °C to quench the reaction. After warming the reaction mixture to room temperature, saturated saline (200 mL) and ethyl acetate (EtOAc) (150 mL) were added to separate the organic and aqueous layers. The aqueous layer was extracted with ethyl acetate (3 x 100 mL) and the organic phases were combined, dried over anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent. The crude product was purified by silica gel column chromatography (SiO2, 80 g, elution gradient 0-8% methanol in ethyl acetate solution) to afford 1-(2-aminopyridin-4-yl)ethanone (36) (176 mg, 20% yield) as a yellow powder. Mass spectrum (ESI+) m/z: 137 [M+H]+.
