315-53-7

172033-73-7

315-53-7

General procedure for the synthesis of 1-hydroxy-4-fluoronaphthalene from 4-fluoro-1-naphthaldehyde: 4-fluoro-1-naphthaldehyde (3.1 g, 17.8 mmol) and dichloromethane (80 mL) were added to a 250 mL three-necked flask. To this clarified solution, m-chloroperoxybenzoic acid (MCPBA, 6.7 g, 19.5 mmol, 1.1 eq.) was slowly added at 0 °C in an ice bath. It was observed that the reaction solution gradually changed to a white suspension. The reaction mixture was stirred and naturally warmed to room temperature under nitrogen protection and reacted overnight. After about 18 hours, the reaction mixture was pale yellow in color, 20% aqueous sodium thiosulfate (40 mL) was added and stirred for 45 minutes at room temperature. 20% aqueous sodium thiosulfate solution (30 mL) was added again and the mixture was transferred to a partition funnel. The organic and aqueous phases were separated and the aqueous phase was back-extracted with dichloromethane (3 x 50 mL). The organic phases were combined and washed sequentially with 20% aqueous sodium thiosulfate (2 x 40 mL) and saturated aqueous sodium chloride (80 mL). The organic phase was concentrated under reduced pressure to give an off-white solid residue. The residue was dissolved in a solvent mixture of methanol (50 mL) and tetrahydrofuran (50 mL) and cooled to 0 °C in an ice bath. To the mixture, 3.0 M potassium hydroxide methanol solution (30 mL) was slowly added, and the rate of addition was controlled so that the reaction temperature was below 5 °C, and the color of the solution gradually changed from light yellow to dark brown. After addition, the reaction mixture was continued to be stirred at 0°C for 30 min. The pH of the reaction solution was adjusted to 1 with concentrated hydrochloric acid (8.0 mL), the solution turned yellow, and stirring was continued for 1 hour. The reaction solution was diluted with water (50 mL) and transferred to a separatory funnel and the aqueous phase was extracted with dichloromethane (3 x 80 mL). The organic phases were combined and washed with water and saturated aqueous sodium chloride solution (180 mL each), respectively. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give a beige solid crude product. The crude product was purified by Biotage Fast Chromatography System (elution gradient: 5% to 50% dichloromethane/hexane) to give 1.51 g (54% yield) of the target compound 1-hydroxy-4-fluoronaphthalene as a tan solid.