Hydrochloric Acid → Ethyl 2-(4-(cyclopropylsulfonyl)phenyl)acetate

Participants

Reaction Steps

To a solution of ethyl [4-(cyclopropylsulfonyl)phenyl](oxo)acetate (20.1 g) in a mixed solvent of tetrahydrofuran (140 mL) and methanol (70 mL) was added 2M aqueous sodium hydroxide solution (70 mL), and the mixture was stirred at room temperature for 16 hr. The reaction mixture was acidified with 1M hydrochloric acid and extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was cooled to −78° C., hydrazine monohydrate (17.3 mL) was added, and the mixture was warmed to room temperature by stirring. The reaction mixture was stirred at 80° C. for 10 min and cooled to room temperature. Potassium hydroxide (12.0 g) was added to the reaction mixture, and the mixture was stirred at 100° C. for 16 hr. Water was added to the reaction mixture, and the aqueous layer was washed with diethyl ether. The aqueous layer was acidified with 1M hydrochloric acid, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. To a solution of the residue in ethanol (500 mL) was added thionyl chloride (6.23 mL) under ice-cooling, and the mixture was warmed to room temperature and stirred at room temperature for 16 hr. The reaction mixture was concentrated under reduced pressure, and the residue was recrystallized from hexane-ether to give the title compound (13.7 g, yield 72%) as colorless crystals. melting point 102-104° C.

Provenance & Evidence