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

HRID 1049953Notes

Reaction equation

HRID 1049953 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[Li].O.[O:20]=[C:21]1[O:25][C@H:24]2[CH2:26][C@@H:27]([O:31][CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[C@H:28]([CH:29]=O)[C@H:23]2[CH2:22]1.[NH4+].[Cl-]>CC(OC)(C)C.ClCCl.O>[F:15][C:9]([F:14])([CH2:10][CH2:11][CH2:12][CH3:13])[C:8](=[O:16])/[CH:7]=[CH:29]/[C@@H:28]1[C@@H:23]2[C@@H:24]([O:25][C:21](=[O:20])[CH2:22]2)[CH2:26][C@H:27]1[O:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 168937Lithium hydroxide, monohydrateHCID 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 56%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

To a solution of dimethyl(3,3-difluoro-2-oxoheptyl)phosphonate (6.9 g, 26.5 mmoL) in MTBE (30 mL) was added LiOH.H2O (1.11 g, 26.5 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 (6, R1 is phenyl, and R2 and R3 are H, 6 g, 23.1 mmoL) in dichloromethane (30 mL) was added followed by NH4Cl (370 mg, 6.93 mmoL), 0.2 mL water and then the mixture was stirred for 12 h. After completion of the reaction, the reaction was then quenched with a saturated NH4Cl solution (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 56% yield.

Workup

  1. stirringthe mixture was stirred for 12 h
  2. customAfter completion of the reaction
  3. customthe reaction was then quenched with a saturated NH4Cl solution (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-706dbbfce2b84e189aa664d8988704f4
Source dataset
uspto-grants-2016_07
Patent number
US09382272B2

Reaction notes

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