Synthesis
General procedure for the synthesis of methyl 3-bromo-2-oxo-2H-pyran-5-carboxylate from methyl coumalate: Pyridine tribromide (8.09 g, 25.3 mmol, 1.3 eq.) and a stirrer were added to a 50 mL round-bottomed flask equipped with a charging funnel. Methyl coumalate (3.0 g, 19.5 mmol, 1 eq.) was placed in the addition funnel. The system was evacuated three times and backfilled with argon. Seventeen mL of acetic acid was added to the flask and 10 mL of acetic acid was added to the addition funnel. The reaction flask was heated to reflux. A solution of methyl coumalate in acetic acid was added slowly and dropwise. After 4 hours of reaction, cool to room temperature and dilute the reaction mixture with deionized water. The organic and aqueous layers were separated by solvent extraction with a 1:1 ethyl acetate/hexane mixture. The organic layer was washed sequentially with deionized water (twice) and saturated saline (once) and then dried over anhydrous sodium sulfate. The desiccant was removed by filtration and the organic solvent was removed by rotary evaporation. The resulting crude product was carefully diluted with saturated aqueous sodium bicarbonate. The precipitated solid was collected by vacuum filtration. The filter cake was ground with additional sodium bicarbonate and water and dried to give 3.76 g (16.1 mmol, 83% yield) of the target product, methyl 3-bromo-2-oxo-2H-pyran-5-carboxylate, as a light yellow solid. Mass spectrometry (ESI+) analysis showed m/z = 233/235 [M+H]+.
References
[1] Patent: US2016/168140, 2016, A1. Location in patent: Paragraph 1172
[2] Patent: WO2004/792, 2003, A1. Location in patent: Page 16
[3] Organic Process Research and Development, 2003, vol. 7, # 1, p. 74 - 81
[4] Chemische Berichte, 1901, vol. 34, p. 1994
[5] Tetrahedron Letters, 1997, vol. 38, # 30, p. 5375 - 5378
