Lithium hydroxide, monohydrate → HCID 59514704, compound

HRID 1943065Notes

Reaction equation

HRID 1943065 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]/[CH:30]=[CH: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]>COC(C)(C)C.O>[C:20]([O:23][C@@H:24]1[C@H:28]([CH2:29]/[CH:30]=[CH: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

6

Reactant 3

HCID 168937Lithium hydroxide, monohydrateHCID 11118722Dimethyl (3,3-difluoro-2-oxoheptyl)phosphonateHCID 11811373HCID 11811373, compound

Product 1

HCID 59514704HCID 59514704, compoundYield 86.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 15413tert-Butyl methyl etherSolvent2×

Procedure

To a solution of dimethyl (3,3-difluoro-2-oxoheptyl)phosphonate (1) (1.816 g, 7.033 mmol) in t-butyl methyl ether (16 ml), lithium hydroxide monohydrate (0.271 g, 6.46 mmol) was added and the mixture was stirred for 2.25 hours at room temperature. A solution of methyl (Z)-7-[(1R,2R,3R,5S)-5-acetoxy-2-formyl-3-(2-tetrahydropyranyl-oxy)cyclopentyl]-5-heptenate (8) (1.554 g, 3.920 mmol) in t-butyl methyl ether (4.7 ml) and water (0.75 ml) were added thereto, and the mixed solution was heat refluxed for approximately 24 hours. After cooling to room temperature, water was added to the solution and the mixture 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 dried with anhydrous magnesium sulfate. After concentration under reduced pressure, the residue was purified by silica gel column chromatography (Fuji Silysia BW-300SP: 47 g, ethyl acetate:hexane=1:4), to give methyl(Z)-7-[(1R,2R,3R,5S)-5-acetoxy-2-((E)-4,4-difluoro-3-oxo-1-octenyl)-3-(2-tetrahydropyranyloxy)cyclopentyl]-5-heptenate (9) (1.787 g; 3.380 mmol; yield: 86.2%) as a pale yellow oil.

Workup

  1. temperaturethe mixed solution was heat
  2. temperaturerefluxed for approximately 24 hours
  3. temperatureAfter cooling to room temperature
  4. stirringthe mixture was stirred
  5. customseparated into two layers
  6. extractionThe aqueous layer was extracted twice with ethyl acetate
  7. washsequentially washed with 3% aqueous sodium chloride and saturated aqueous sodium chloride
  8. dry with materialdried with anhydrous magnesium sulfate
  9. concentrationAfter concentration under reduced pressure
  10. customthe residue was purified by silica gel column chromatography (Fuji Silysia BW-300SP: 47 g, ethyl acetate:hexane=1:4)

Sources & evidence

ORD record
ord-727972d7093545d88a913e62f09ee804
Source dataset
uspto-grants-2013_03
Patent number
US08389748B2

Reaction notes

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