Water → methyl 7-[(1R,2R,3R,5S)-5-acetoxy-2-((E)-4,4-difluoro-3-oxo-1-octenyl)-3-(2-tetrahydropyranyloxy)cyclopentyl]heptanate

HRID 1159570Notes

Reaction equation

HRID 1159570 reaction equation
[F:1][C:2]([F:16])([CH2:12][CH2:13][CH2:14][CH3:15])[C:3](=[O:11])[CH2:4]P(=O)(OC)OC.O.[OH-].[Li+].[C:20]([O:23][C@@H:24]1[C@H:28]([CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][C:35]([O:37][CH3:38])=[O:36])[C@@H:27]([CH:39]=O)[C@H:26]([O:41][CH:42]2[CH2:47][CH2:46][CH2:45][CH2:44][O:43]2)[CH2:25]1)(=[O:22])[CH3:21].O>O1CCCC1>[C:20]([O:23][C@@H:24]1[C@H:28]([CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][C:35]([O:37][CH3:38])=[O:36])[C@@H:27](/[CH:39]=[CH:4]/[C:3](=[O:11])[C:2]([F:1])([F:16])[CH2:12][CH2:13][CH2:14][CH3:15])[C@H:26]([O:41][CH:42]2[CH2:47][CH2:46][CH2:45][CH2:44][O:43]2)[CH2:25]1)(=[O:22])[CH3:21]

Participants

6

Reactant 4

HCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 11118722Dimethyl (3,3-difluoro-2-oxoheptyl)phosphonateHCID 11729034methyl 7-[(1R,2R,3R,5S)-5-acetoxy-2-formyl-3-(2-tetrahydropyranyl-oxy)cyclopentyl]heptanate

Product 1

HCID 59514691methyl 7-[(1R,2R,3R,5S)-5-acetoxy-2-((E)-4,4-difluoro-3-oxo-1-octenyl)-3-(2-tetrahydropyranyloxy)cyclopentyl]heptanateYield 55.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of dimethyl (3,3-difluoro-2-oxoheptyl)phosphonate (1) (1.110 g, 4.299 mmol) in tetrahydrofuran (17 ml) was added with lithium hydroxide monohydrate (0.171 g, 4.08 mmol), and the mixture was stirred for approximately 1.2 hours at room temperature. A solution of methyl 7-[(1R,2R,3R,5S)-5-acetoxy-2-formyl-3-(2-tetrahydro pyranyloxy)cyclopentyl]heptanate (2) (0.971 g, 2.44 mmol) in tetrahydrofuran (3 ml), and water (0.32 ml) were added thereto, and the mixed solution was heat refluxed for approximately 48 hours. After cooling to room temperature, the solution was concentrated under reduced pressure. Ethyl acetate and water were added to the residue and the solution was stirred, let to stand and then separated into two layers. The aqueous layer was extracted twice with ethyl acetate. The organic layers were combined, sequentially washed with 3% aqueous sodium chloride and saturated aqueous sodium chloride, and then dried with anhydrous magnesium -sulfate. After concentration under reduced pressure, the residue was purified by silica gel column chromatography (Fuji Silysia BW-300SP: 38 g; ethyl acetate:hexane=1:4), to give methyl 7-[(1R,2R,3R,5S)-5-acetoxy-2-((E)-4,4-difluoro-3-oxo-1-octenyl)-3-(2-tetrahydropyranyloxy)cyclopentyl]heptanate (3) (0.722 g; 1.36 mmol; yield: 55.8%).

Workup

  1. temperaturethe mixed solution was heat
  2. temperaturerefluxed for approximately 48 hours
  3. temperatureAfter cooling to room temperature
  4. concentrationthe solution was concentrated under reduced pressure
  5. additionEthyl acetate and water were added to the residue
  6. stirringthe solution was stirred
  7. customseparated into two layers
  8. extractionThe aqueous layer was extracted twice with ethyl acetate
  9. washsequentially washed with 3% aqueous sodium chloride and saturated aqueous sodium chloride
  10. dry with materialdried with anhydrous magnesium -sulfate
  11. concentrationAfter concentration under reduced pressure
  12. customthe residue was purified by silica gel column chromatography (Fuji Silysia BW-300SP: 38 g; ethyl acetate:hexane=1:4)

Sources & evidence

ORD record
ord-8cf2ea7cd41c41f3ac4a047634899e01
Source dataset
uspto-grants-2010_10
Patent number
US07812182B2

Reaction notes

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