1-Fluoro-3-(methoxymethoxy)benzene

372-20-3

107-30-2

126940-10-1

The general procedure for the synthesis of 1-fluoro-3-(methoxymethoxy)benzene from 3-fluorophenol and chloromethyl methyl ether is as follows: 100 g (0.892 mol) of 3-fluorophenol is dissolved in 800 ml of dichloromethane and the solution is cooled to -10 °C. To this solution 155 g (1.20 mol) of diisopropylethylamine was slowly added dropwise over a period of 15 minutes. Upon completion of the dropwise addition, the addition funnel was rinsed with 100 mL of dichloromethane to flush the residual diisopropylethylamine into the reaction mixture. Subsequently, 100 g (1.24 mol) of chloromethyl methyl ether was added dropwise to the reaction mixture, and the titration rate was controlled to maintain the reaction temperature between -10°C and 2°C. After completion of dropwise addition, the reaction mixture was gradually warmed to room temperature and stirring was continued for 22 hours. Upon completion of the reaction, the reaction mixture was quenched with 500 mL of water. The organic phase was separated and washed sequentially with 500 ml of 2 M aqueous sodium bisulfate and 300 ml of 1 M aqueous sodium hydroxide. The organic phase was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give 130 g of a yellow oily crude product. Finally, the crude product was purified by Kugelrohr distillation (80 °C, 0.1 Torr) to give 126 g (91% yield) of the target compound 1-fluoro-3-(methoxymethoxy)benzene as a colorless oil.