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

HRID 1874100Notes

Reaction equation

HRID 1874100 reaction equation
COP([CH2:7][C:8](=[O:16])[C:9]([F:15])([F:14])[CH2:10][CH2:11][CH2:12][CH3:13])(=O)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]>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:7]/[C:8](=[O:16])[C:9]([F:14])([F:15])[CH2:10][CH2:11][CH2:12][CH3:13])[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

5

Reactant 3

HCID 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 40.4%

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-tetrahydropyranyloxy)cyclopentyl]heptanate (2) (0.962 g, 2.41 mmol) in tetrahydrofuran (3 ml) was 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 stirred, then, the mixture was let to stand and 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) (0.517 g; 0.973 mmol; yield: 40.4%).

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. stirringstirred
  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-a5ec65c6fe6044a39ce9a0d39b1d8fe0
Source dataset
uspto-grants-2012_11
Patent number
US08304562B2

Reaction notes

Loading…