Synthesis
General procedure for the synthesis of 8-fluorobenzodihydropyran-4-one from 3-(2-fluorophenoxy)propionic acid: oxalyl chloride (8.79 mL) and 1 drop of N,N-dimethylformamide (DMF) were added to a solution of 3-(2-fluorophenoxy)propionic acid (9.27 g) in dichloromethane (DCM, 50 mL) under ice-bath conditions. The reaction mixture was stirred at 0 °C for 2 h. Aluminum chloride (7.39 g, 55.42 mmol) was subsequently added. The reaction mixture was continued to be stirred at room temperature for 16 hours. After completion of the reaction, the mixture was poured into ice water and extracted three times with dichloromethane (DCM). The organic phases were combined and washed sequentially with 0.5 M sodium hydroxide (NaOH) solution and saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography with the eluent of 20% ethyl acetate (EtOAc)/hexane (Hex) to afford the target product 8-fluorobenzodihydropyran-4-one (8.20 g, 98% yield).
References
[1] Patent: WO2006/108103, 2006, A1. Location in patent: Page/Page column 95; 96
[2] Patent: US2008/119496, 2008, A1. Location in patent: Page/Page column 12; 30
[3] Journal of Medicinal Chemistry, 1988, vol. 31, # 1, p. 230 - 243
[4] Patent: EP2913330, 2015, A1. Location in patent: Paragraph 0653
[5] Patent: WO2006/66950, 2006, A2. Location in patent: Page/Page column 33-36
