Synthesis
5-Fluoro-2-hydroxyacetophenone (1.54 g, 10 mmol) and diethyl carbonate (2.42 mL, 20 mmol) were dissolved in anhydrous tetrahydrofuran (30 mL) in a dry flask. The above solution was added dropwise to a rapidly stirred solution of potassium tert-butanolate tetrahydrofuran (1.0 M, 30 mL) through a cannula. The reaction was stirred overnight (10 hours) at room temperature and under positive pressure protection with nitrogen. Upon completion of the reaction, the crude product was concentrated under reduced pressure and partitioned between methyl tert-butyl ether and water. The layers were separated and the organic phase was discarded. The aqueous phase was adjusted to pH 5 with hydrochloric acid and subsequently extracted three times with an equal volume of dichloromethane. The organic phases were combined, dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford 6-fluoro-4-hydroxy-2H-benzopyran-2-one (1.4 g, 78% yield). Mass spectrum (ESI negative ion mode) m/e: 179.16 ([M-H]-).
References
[1] Journal of Medicinal Chemistry, 2009, vol. 52, # 22, p. 7142 - 7156
[2] Patent: WO2009/100250, 2009, A1. Location in patent: Page/Page column 57
[3] Organic and Biomolecular Chemistry, 2018, vol. 16, # 15, p. 2634 - 2638
[4] Patent: EP354693, 1990, A1
[5] Advanced Synthesis and Catalysis, 2013, vol. 355, # 13, p. 2550 - 2557
