Acetic Acid → methyl 7-[(1R,2R,3R,5S)-5-acetoxy-2-((6S)-4,4-difluoro-6-methyl-3-hydroxyoctyl)-3-(2-tetrahydropyranyloxy)cyclopentyl]heptanate

HRID 593324Notes

Reaction equation

HRID 593324 reaction equation
[C:1]([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][CH3:19])=[O:17])[C@@H:8]([CH2:20][CH2:21][C:22](=[O: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:3])[CH3:2].[BH4-].[Na+].C(O)(=O)C>CO>[C:1]([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][CH3:19])=[O:17])[C@@H:8]([CH2:20][CH2:21][CH:22]([OH:31])[C:23]([F:29])([F:30])[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:3])[CH3:2]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 4311764Sodium borohydrideHCID 71149713methyl 7-[(1R,2R,3R,5S)-5-acetoxy-2-((6S)-4,4-difluoro-6-methyl-3-oxooctyl)-3-(2-tetrahydropyranyloxy)cyclopentyl]heptanate

Product 1

HCID 71150072methyl 7-[(1R,2R,3R,5S)-5-acetoxy-2-((6S)-4,4-difluoro-6-methyl-3-hydroxyoctyl)-3-(2-tetrahydropyranyloxy)cyclopentyl]heptanateYield 100.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of methyl 7-[(1R,2R,3R,5S)-5-acetoxy-2-((6S)-4,4-difluoro-6-methyl-3-oxooctyl)-3-(2-tetrahydro pyranyloxy)cyclopentyl]heptanate (D) (72.56 g, 132.7=1) in methanol (290 ml) was cooled to approximately −20° C., and sodium borohydride (5.00 g, 132.2 mmol) was added thereto. After stirring for approximately 35 minutes, acetic acid (7.5 ml, 131=1) was added dropwise, and the reaction mixture was concentrated under reduced pressure. The residue was supplemented with water (326 ml) and extracted three times with ethyl acetate (226 ml). The organic layers were combined, washed with 3% aqueous sodium chloride (323 ml) and saturated aqueous sodium chloride (323 ml), and dried with anhydrous magnesium sulfate (40.6 g). The solution was concentrated under reduced pressure to give methyl 7-[(1R,2R,3R,5S)-5-acetoxy-2-((6S)-4,4-difluoro-6-methyl-3-hydroxyoctyl)-3-(2-tetrahydropyranyloxy)cyclopentyl]heptanate (E) (73.01 g; quantitative yield) as a colorless oil.

Workup

  1. concentrationthe reaction mixture was concentrated under reduced pressure
  2. extractionextracted three times with ethyl acetate (226 ml)
  3. washwashed with 3% aqueous sodium chloride (323 ml) and saturated aqueous sodium chloride (323 ml)
  4. dry with materialdried with anhydrous magnesium sulfate (40.6 g)
  5. concentrationThe solution was concentrated under reduced pressure

Sources & evidence

ORD record
ord-4c926d85d3de4f038b665b537530e76d
Source dataset
uspto-grants-2016_01
Patent number
US09242950B2

Reaction notes

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