Uses
3,6-Dihydro-1(2H)-pyridinecarboxylic Acid Phenylmethyl Ester is used in the synthesis of potent antibacterials targeting type IIA topoisomerases. Also used in the synthesis of inhibitors of papain-like cathespin proteases.
Synthesis
General procedure: A mixed solution of 1,2,5,6-tetrahydropyridine (36.1 g, 1 eq.), sodium carbonate (1.5 eq.) and water (45 eq.) was cooled in an ice water bath. Benzyl chloroformate (1.1 eq.) was slowly added dropwise over a period of 1 h. The reaction was kept at 5 °C for 2 h. The reaction was then slowly warmed to room temperature and continued for 16 h. The reaction was completed with the addition of saturated table water. After completion of the reaction, the reaction mixture was diluted with saturated saline and the product was extracted with ethyl acetate (EtOAc). The organic layer was dried over anhydrous sodium sulfate (Na2SO4) and concentrated under reduced pressure to give an oily crude product. The crude product was purified by fast column chromatography (elution gradient: 10% ethyl acetate/hexane to 100% ethyl acetate) to afford the target compound benzyl 5,6-dihydropyridine-1(2H)-carboxylate (36.2, 99% yield) as a colorless oil.EIMS (m/z): calculated value of C13H15NO2 (M++1) 218.26, measured value 218.10 EIMS (m/z).
References
[1] Tetrahedron Letters, 2002, vol. 43, # 23, p. 4289 - 4293
[2] Journal of Organic Chemistry, 1991, vol. 56, # 9, p. 3133 - 3137
[3] Patent: WO2011/29046, 2011, A1. Location in patent: Page/Page column 193
[4] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 5, p. 1254 - 1259
[5] Tetrahedron, 2006, vol. 62, # 14, p. 3284 - 3291
