Preparative Example 23: Synthesis of 3-methylpiperidine-2,6-dione
Acetic anhydride (appropriate amount) was added to commercially available 2-methylglutaric acid (1 g, 6.8 mmol) at room temperature, and the mixture was refluxed and stirred at 60°C for 8 hours. After confirming the completion of the reaction by thin layer chromatography (TLC), the remaining acetic anhydride was removed under reduced pressure. The concentrated compound was dissolved in tetrahydrofuran (THF) and aqueous ammonia solution (1.7 mL, 14.6 mmol) was slowly added at 0 °C, followed by stirring for 8 h at room temperature. Upon completion of the reaction, the remaining ammonia solution was removed under reduced pressure, acetic anhydride was added, and then refluxed at 60 °C for 8 hours. The residual acetic anhydride was removed under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate/hexane=1:1) to afford 682 mg (yield: 78%) of 3-methylpiperidine-2,6-dione.
1H NMR (400 MHz, MeOH-d4) δ 1.24-1.28 (m, 3H), 1.71-1.77 (m, 1H), 2.04-2.08 (m, 1H), 2.57-2.65 (m, 3H); MS (m/z) 128 (M+1).
