Water → HCID 86612722, compound

Participants

Reaction Conditions

Reaction Steps

65.3 g of ethyl (2S)-3-{3-[(2R)-3-(4-chloro-2-cyanophenoxy)-2-hydroxypropoxy]phenyl}-2-isopropoxypropionate was dissolved in 1.3L of dichloromethane, which was then cooled to −68° C. Then 54 mL of diethylaminosulfur trifluoride was added, followed by stirring at room temperature for 4 days. The reaction mixture was cooled with ice, to which water (1 L) and a saturated sodium chloride solution (1 L) were then added, followed by extraction with ethyl acetate (4 L). The organic layer was washed with the saturated sodium chloride solution (2 L) and dried with anhydrous magnesium sulfate, followed by distilling off the solvent under a reduced pressure. The residue was purified using silica gel column chromatography to obtain 33 g of ethyl (2S)-3-[3-[(2S)-3-(4-chloro-2-cyanophenoxy)-2-fluoropropoxy]phenyl]-2-isopropoxypropionate from a hexane-ethyl acetate (7:1→5:1)-eluted fraction. This compound was dissolved in 400 mL of ethanol, to which 107 mL of 2N sodium hydroxide aqueous solution was then added, followed by stirring the reaction mixture at room temperature for 2 hours. The reaction mixture was cooled with ice, to which water (500 mL) and a 5N hydrochloric acid aqueous solution (50 mL) were then added before further adding water (1 L), followed by extraction with ethyl acetate (2.5 L). The organic layer was washed with the saturated sodium chloride solution (1 L) and dried with anhydrous magnesium sulfate, followed by distilling off the solvent under a reduced pressure. The residue was purified using silica gel column chromatography to obtain 27.6 g of the title compound in the form of colorless oily matter from a hexane-ethyl acetate (3:1→1:1)-eluted fraction.

Provenance & Evidence