2-Fluoroethyl bromide → 4-(2-Fluoroethoxymethyl)phenyl 2-fluoroethyl ether

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Reaction Steps

To a stirred solution of 5.0 grams (0.029 mole) of 2-fluoroethyl 4-hydroxymethylphenyl ether in 50 ml of tetrahydrofuran was added 15 ml of a 50% aqueous, sodium hydroxide solution, 7.6 grams (0.060 mole) of 1-bromo-2-fluoroethane, and 0.78 gram (0.0023 mole) of tetrabutylammonium hydrogen sulfate. The resultant mixture was stirred and heated at reflux for approximately 18 hours. The mixture was cooled and was extracted with diethyl ether. The extract was washed in succession with a dilute, aqueous, sodium hydroxide solution, an aqueous 10% lithium chloride solution, and a saturated, aqueous, sodium chloride solution. The washed organic phase was dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated under reduced pressure to leave an oil. Analysis of this oil by nmr indicated a large amount of starting material remained. The oil was again heated at reflux with the same quantities of the above reactants for 30 minutes. The reaction mixture was cooled and extracted with diethyl ether. The extract was washed several times with water followed by an aqueous, 15% lithium chloride solution. The washed extract was dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated under reduced pressure leaving an oil. Analysis of this oil by nmr indicated starting material was still present. This oil was heated at reflux with the same quantities of the above reagents for approximately 24 hours. The mixture was cooled and extracted with diethyl ether. The extract was washed with water and was dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated under reduced pressure to yield 1.9 grams of 4-(2-fluoroethoxymethyl)phenyl 2-fluoroethyl ether as an oil.

Provenance & Evidence