40473-07-2

Light yellow liquid

The commercial 2-Bromo-6-methoxypyridine could be used as a starting material to synthesize cyclopenta[b]pyridin-2,5-dione. The overall route consists of a first sequence of regioselective ortho lithiation and methoxycarbonylation followed by Heck vinylation, alkene reduction, cyclization, and decarboxylation[1].

Under argon protection, sodium methanol (1.82 g) was slowly added to a solution of toluene (120 mL) containing 2,6-dibromopyridine (8.0 g), followed by continuous stirring at 120 °C for 13 hours. During the reaction, sodium methanol (0.728 g) was added supplementally and stirring was continued at the same temperature for 6 hours. Upon completion of the reaction, the mixture was naturally cooled to room temperature. The reaction mixture was transferred to a dispensing funnel and partitioned by adding water and ethyl acetate. The organic layer was separated, dried with anhydrous sodium sulfate, filtered and the solvent was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate gradient) to afford 2-bromo-6-methoxypyridine as an oil (5.64 g, 89% yield). The structure of the product was confirmed by 1H-NMR (400 MHz, CDCl3): δ 3.93 (3H, s, OCH3), 6.68 (1H, d, J = 8.0 Hz, Ar-H), 7.05 (1H, d, J = 7.2 Hz, Ar-H), 7.39-7.42 (1H, m, Ar-H).

[1] Robert, Nicolas , et al. "A convenient synthesis of cyclopenta[b]pyridin-2,5-dione as a non- glycosidic cardiotonic agent." ARKIVOC 2008.7(2008):92-100.