Uses
Diethyl 4-Chloropyridine-2,6-dicarboxylate is a chemical reagent used in the synthesis of luminescent lanthanide complexes. Also used in the production of metal chelating inhibitors against fructose 1,6-bisphosphate (FBP) aldolase in the treatment of infectious bacteria and fungi.
Synthesis
The crude 4-chloropyridine-2,6-dicarbonyl dichloride was dissolved in dichloromethane (100 mL) under cooling conditions in an ice bath, followed by the slow addition of a mixture of pyridine (6 mL) and ethanol (5 mL). The reaction mixture was stirred in an ice bath for 5 minutes, then removed from the ice bath and continued to stir at room temperature for 5 hours. Upon completion of the reaction, the volatile solvent was removed by distillation under reduced pressure. The residue was washed with a mixture of 1 M hydrochloric acid (30 mL) and saturated aqueous sodium chloride solution (50 mL) and subsequently extracted with dichloromethane (200 mL). The organic phases were combined, dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by silica gel fast column chromatography using ethyl acetate-hexane (1:4, subsequently adjusted to 1:3) as eluent to give finally diethyl 4-chloro-2,6-pyridinedicarboxylate (800 mg, 62% yield). The product was characterized by 1H NMR (DMSO-d6): δ 1.36 (t, 6H, J = 7.1 Hz, CH3), 3.33 (s, 3H, CH3), 4.40 (q, 4H, J = 7.1 Hz, CH2), 8.31 (s, 2H, Ar).
References
[1] Patent: US2004/198728, 2004, A1. Location in patent: Page/Page column 8
[2] Canadian Journal of Chemistry, 1991, vol. 69, # 7, p. 1107 - 1116
[3] Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 21, p. 4703 - 4707
[4] Chemical Communications, 2014, vol. 50, # 71, p. 10323 - 10326
