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

HRID 593325Notes

Reaction equation

HRID 593325 reaction equation
C([O:4][C@@H:5]1[C@H:9]([CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][C:16]([O:18]C)=[O:17])[C@@H:8]([CH2:20][CH2:21][CH:22]([OH:31])[C:23]([F:30])([F:29])[CH2:24][C@@H:25]([CH3:28])[CH2:26][CH3:27])[C@H:7]([O:32][CH:33]2[CH2:38][CH2:37][CH2:36][CH2:35][O:34]2)[CH2:6]1)(=O)C.[OH-].[Na+]>C(O)C>[F:30][C:23]([F:29])([CH2:24][C@@H:25]([CH3:28])[CH2:26][CH3:27])[CH:22]([OH:31])[CH2:21][CH2:20][C@H:8]1[C@H:7]([O:32][CH:33]2[CH2:38][CH2:37][CH2:36][CH2:35][O:34]2)[CH2:6][C@H:5]([OH:4])[C@@H:9]1[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][C:16]([OH:18])=[O:17]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 71150072methyl 7-[(1R,2R,3R,5S)-5-acetoxy-2-((6S)-4,4-difluoro-6-methyl-3-hydroxyoctyl)-3-(2-tetrahydropyranyloxy)cyclopentyl]heptanate

Product 1

HCID 711499027[(1R,2R,3R,5S)-2-((6S)-4,4-difluoro-6-methyl-3-hydroxyoctyl)-5-hydroxy-3-(2-tetrahydropyranyloxy)cyclopentyl]heptanoic acid

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

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.

Workup

  1. concentrationthe reaction mixture was concentrated under reduced pressure
  2. additionThe residue was mixed with water (281 ml) and t-butyl methyl ether (141 ml)
  3. temperaturecooled on ice
  4. additionAfter 6M-hydrochloric acid was added dropwise
  5. extractionthe solution was extracted three times with ethyl acetate (281 ml)
  6. washsequentially washed with water (281 ml) twice
  7. dry with materialAfter drying with anhydrous magnesium sulfate (50 g)
  8. concentrationthe solution was concentrated under reduced pressure

Sources & evidence

ORD record
ord-7203b24a810e4d6abe36d195cf31a6d1
Source dataset
uspto-grants-2016_01
Patent number
US09242950B2

Reaction notes

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