Hydrochloric Acid → 10-[(3S,4S)-7-hydroxy-3-(4-hydroxyphenyl)-3-methylthiochroman-4-yl]-2-(4,4,5,5,5-pentafluoropentyl)decanoic acid

Participants

Reaction Conditions

Reaction Steps

A solution of potassium hydroxide (22.35 g, 398.4 mmol) in water (70 ml) was added to a solution of dimethyl 2-{8-[(3S,4S)-7-methoxy-3-(4-methoxyphenyl)-3-methylthiochroman-4-yl]octyl}-2-(4,4,5,5,5-pentafluoropentyl)malonate (7.0 g, 9.96 mmol) in ethanol (140 ml), followed by heating under reflux for 15 hours. The reaction mixture was adjusted to pH 4 by addition of hydrochloric acid at 0° C. and then concentrated under reduced pressure. Water was added to the residue, which was then extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate. After distilling off the solvent, a solution of boron tribromide in dichloromethane (1N, 59.76 ml, 59.76 mmol) was added to a solution of the residue in dichloromethane (100 ml) at −78° C. The resulting mixture was stirred and warmed to 0° C. over 3 hours. Water was added to the reaction mixture, which was then extracted with dichloromethane. The organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. After distilling off the solvent, toluene (50 ml) was added to the residue, followed by heating under reflux for 72 hours. Water was added to the reaction mixture, which was then extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. After distilling off the solvent, the residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate/dichloromethane=5/1/1) to give 10-[(3S,4S)-7-hydroxy-3-(4-hydroxyphenyl)-3-methylthiochroman-4-yl]-2-(4,4,5,5,5-pentafluoropentyl)decanoic acid (3.4 g, Yield 57.8%).

Provenance & Evidence