Dimethyl (3,3-difluoro-2-oxoheptyl)phosphonate → (3aR,4R,5R,6aS)-4-((E)-4,4-difluoro-3-oxo-1-octenyI)-2-oxo-5-(phenylmethoxy)hexahydro-2H-cyclopenta[b]furan

HRID 1049954Notes

Reaction equation

HRID 1049954 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:17]=[C:18]1[O:22][C@H:21]2[CH2:23][C@@H:24]([O:28][CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[C@H:25]([CH:26]=O)[C@H:20]2[CH2:19]1>CC(OC)(C)C.O.ClCCl.[Zn](O)O>[F:15][C:9]([F:14])([CH2:10][CH2:11][CH2:12][CH3:13])[C:8](=[O:16])/[CH:7]=[CH:26]/[C@@H:25]1[C@@H:20]2[C@@H:21]([O:22][C:18](=[O:17])[CH2:19]2)[CH2:23][C@H:24]1[O:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

6

Reactant 2

HCID 11118722Dimethyl (3,3-difluoro-2-oxoheptyl)phosphonateHCID 14460245(3aR,4R,5R,6aS)-hexahydro-2-oxo-5-(phenylmethoxy)-2H-cyclopenta[b]furan-4-carboxaldehyde

Product 1

HCID 46862980(3aR,4R,5R,6aS)-4-((E)-4,4-difluoro-3-oxo-1-octenyI)-2-oxo-5-(phenylmethoxy)hexahydro-2H-cyclopenta[b]furanYield 76%

Reagents, catalysts & solvents 3

HCID 178526214HCID 178526214, compoundCatalystHCID 6344DichloromethaneSolventHCID 23212559water MeOtBuSolvent

Procedure

To a mixture of dimethyl(3,3-difluoro-2-oxoheptyl)phosphonate (210 mg, 0.81 mmoL) in MTBE/H2O (3/0.1 mL) was added Zn(OH)2 (100 mg, 0.81 mmoL) and the mixture was stirred under nitrogen for 1 h. A solution of (3aR,4R,5R,6aS)-hexahydro-2-oxo-5-(phenylmethoxy)-2H-cyclopenta[b]furan-4-carboxaldehyde (200 mg, 0.77 mmoL) in dichloromethane (3 mL) was added and the mixture was stirred for 24 h. After completion of the reaction, the reaction was then quenched with cold 1N HCl (12 mL). The organic layer was separated, washed with brine, dried over Na2SO4 and concentrated to dryness under vacuum. The crude material was further purified by column chromatography [25% ethyl acetate in heptanes] to yield (3aR,4R,5R,6aS)-4-((E)-4,4-difluoro-3-oxo-1-octenyl)-2-oxo-5-(phenylmethoxy)hexahydro-2H-cyclopenta[b]furan (7, R1 is phenyl, and R2 and R3 are H) in 76% yield.

Workup

  1. stirringthe mixture was stirred for 24 h
  2. customAfter completion of the reaction
  3. customthe reaction was then quenched with cold 1N HCl (12 mL)
  4. customThe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated to dryness under vacuum
  8. customThe crude material was further purified by column chromatography [25% ethyl acetate in heptanes]

Sources & evidence

ORD record
ord-51124c6f60614eacb08edd621d6248dc
Source dataset
uspto-grants-2016_07
Patent number
US09382272B2

Reaction notes

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