Sodium Hydroxide → 7[(1R,2R,3R,5S)-2-((6S)-4,4-difluoro-6-methyl-3-hydroxyoctyl)-5-hydroxy-3-(2-tetrahydropyranyloxy)cyclopentyl]heptanoic acid

Participants

Reaction Steps

A solution of methyl 7-[(1R,2R,3R,5S)-5-acetoxy-2-((6S)-4,4-difluoro-6-methyl-3-hydroxyoctyl)-3-(2-tetrahydropyranyloxy)cyclopentyl]heptanate (E) (132.5 mmol) in ethanol (213 ml) was cooled on ice, and an 24% sodium hydroxide aqueous solution (135 ml, 1029 mmol) was added thereto dropwise. After stirring at room temperature for approximately 3.5 hours, the reaction mixture was concentrated under reduced pressure. The residue was mixed with water (281 ml) and t-butyl methyl ether (141 ml), and cooled on ice. After 6M-hydrochloric acid was added dropwise to adjust to pH 3 to 4, the solution was extracted three times with ethyl acetate (281 ml). The organic layers were combined and sequentially washed with water (281 ml) twice and saturated aqueous sodium chloride (338 ml). After drying with anhydrous magnesium sulfate (50 g), the solution was concentrated under reduced pressure to give crude 7[(1R,2R,3R,5S)-2-((6S)-4,4-difluoro-6-methyl-3-hydroxyoctyl)-5-hydroxy-3-(2-tetrahydropyranyloxy)cyclopentyl]heptanoic acid (F) as white solid. The entire amount was used in the following step without purification.

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