1124199-15-0

1124199-14-9

1124199-15-0

1. D-Cbz-nicotinic acid ((R)-piperidine-1,3-dicarboxylic acid 1-benzyl ester) (1.32 g, 5.0 mmol) was dissolved in toluene (25 mL) and DMF (20 μL) was added as a catalyst. Oxalyl chloride (646 μL, 7.5 mmol) was then added slowly and the reaction mixture was stirred at room temperature for 3 hours. Upon completion of the reaction, the solvent was removed by rotary evaporator to give an oily crude product. 2. The above crude acyl chloride was dissolved in THF (20 mL) and cooled to 0-5 °C. A THF solution of 2M methylamine (7.5 mL, 15 mmol) was slowly added under ice bath conditions. The reaction mixture was stirred at low temperature for 2 h, followed by gradual warming to room temperature. The solvent was removed by rotary evaporator to give solid product. The solid was washed with water and filtered to give the Cbz-protected intermediate as a colorless solid (1.25 g, 91% yield).LC/MS analysis showed a retention time of 5.05 min and [M + 1]+ of 277. 3. The Cbz-protected intermediate (1.0 g, 3.62 mmol) was dissolved in EtOH (50 mL) with 10% palladium-carbon catalyst (50% water content, 750 mg). The hydrogenation reaction was carried out under 60-70 psi hydrogen pressure for 5 hours. Upon completion of the reaction, the crude reaction mixture was filtered through diatomaceous earth to remove the catalyst. The filtrate was concentrated by rotary evaporator, redissolved in EtOH (10 mL) and further filtered through a nylon syringe filter to remove residual catalyst. Ultimately, the crude product was obtained as a viscous solid by evaporation of the solvent (581 mg, 113% yield).LC/MS analysis showed a retention time of 0.68 min and [M + 1]+ of 143.