Methanol → Methyl (2-bromo-4-fluorophenyl)acetate

Participants

Reaction Steps

Thionyl chloride (6 mL) was added dropwise to a solution of 2-bromo-4-fluorophenylacetic acid (5.0 g) in methanol (50 mL), and the reaction solution was stirred at room temperature for one hour. The reaction mixture was concentrated under reduced pressure, and then the residue was dissolved in ethyl acetate. The solution was filtered through a silica gel pad (carrier: Chromatorex NH), and the filtrate was concentrated under reduced pressure to obtain methyl 2-bromo-4-fluorophenylacetate (5.53 g). A solution of methyl 2-bromo-4-fluorophenylacetate (2.0 g) in DMF (5 mL) was added to a suspension of sodium hydride (containing mineral oil at 40%, 356 mg) in DMF (20 mL) under ice-cooling. The reaction solution was stirred for 10 minutes, further stirred at room temperature for 30 minutes and then ice-cooled again. A solution of 1-chloro-3-iodopropane (1.82 g) in DMF (5 mL) was added to the reaction mixture, and the reaction solution was stirred at room temperature for three hours. Water and ethyl acetate were added to the reaction mixture, and the organic layer was separated. The resulting organic layer washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. Hydrazine monohydrate (8 mL) was added to a solution of the resulting crude purified methyl 5-chloro-2-(2-bromo-4-fluoro)phenylpentanoate (2.75 g) in ethanol (20 mL), and the reaction solution was heated under reflux for 3.5 hours. The reaction solution was left to cool to room temperature and then concentrated under reduced pressure. Saturated sodium bicarbonate water and ethyl acetate and were added to the residue, and the organic layer was separated. The resulting organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (elution solvent: ethyl acetate-methanol system) to obtain 1.157 g of the title compound. The property values of the compound are as follows.

Provenance & Evidence