Uses
tert-Butyl (2,6-Dioxopiperidin-3-yl)carbamate is an intermediate in the synthesis of Thalidomide-d4 (T338852), a labelled Thalidomide, which inhibits FGF-induced angiogenesis. Inhibits replication of human immunodeficiency virus type 1. Teratogenic sedative.
Synthesis
General procedure for the synthesis of 3-Boc-amino-2,6-dioxopiperidine from BOC-L-glutamine: N-(tert-butoxycarbonyl)-L-glutamine (4.92 g, 20 mmol) and carbonyldiimidazole (1.70 g, 10.5 mmol) were dissolved in tetrahydrofuran (100 mL) and heated to reflux for 9 hours. After completion of the reaction, the solvent was removed by distillation under reduced pressure to give the crude product. The crude product was recrystallized from hot ethyl acetate to afford the target compound 3-Boc-amino-2,6-dioxopiperidine (2.04 g, 45% yield) as white crystals. Melting point: 214-215 °C; 1H NMR (DMSO-d6) δ 4.22 (dd, J = 6.2 Hz, J = 11.0 Hz, 1H), 2.77-2.65 (m, 1H), 2.45 (m, 1H), 1.96-1.87 (m, 2H), 1.40 (s, 9H); mass spectrum (CI/CH4) m/z 227 [M-1 ]+.
References
[1] Organic Letters, 2003, vol. 5, # 16, p. 2865 - 2867
[2] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 21, p. 5819 - 5824
[3] Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 2, p. 650 - 662
[4] Patent: WO2005/28436, 2005, A2. Location in patent: Page/Page column 30; 53
[5] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 21, p. 5260 - 5262
