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 1049954노트

반응식

HRID 1049954 반응식
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

참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 178526214HCID 178526214, 화합물촉매HCID 6344Dichloromethane용매HCID 23212559water MeOtBu용매

실험 절차

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.

후처리

  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]

출처 및 근거

ORD 기록
ord-51124c6f60614eacb08edd621d6248dc
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09382272B2

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