The general procedure for the synthesis of tert-butyl (4-formylpyridin-3-yl) carbamate from N-formylpiperidine was as follows: tert-butylpyridin-3-yl carbamate (17.7 g, 91.1 mmol) was dissolved in THF (300 mL) and the solution was cooled to -78 °C. A pentane solution of 1.70 M tert-butyllithium (129 mL) was slowly added with stirring. After addition, the reaction mixture was continued to be stirred at -78 °C for 15 minutes, followed by warming to -20 °C and stirring for 1.5 hours. Keeping the temperature below -15 °C, 1-piperidinecarboxaldehyde (30.4 mL, 0.273 mol) was added dropwise to the reaction mixture. After the dropwise addition was completed, the reaction mixture was brought to room temperature and stirred overnight. Upon completion of the reaction, the mixture was cooled to 0 °C and the pH was adjusted to 2 by slow addition of 1 M HCl solution.Subsequently, solid Na2CO3 was added to adjust the pH to 7. The reaction mixture was extracted three times with ethyl acetate and the organic phases were combined. The organic phase was washed sequentially with water (three times) and saturated saline. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography (eluent: 50% ethyl acetate/hexane) to afford the target product (4-formylpyridin-3-yl)carbamic acid tert-butyl ester as a yellow solid (12.2 g, 60% yield).LCMS analysis: m/z = 223.1 for C11H15N2O3 ([M+H]+).
