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 1049954ノート

反応式

HRID 1049954 の反応式
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

参加物

6

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 178526214HCID 178526214、化合物触媒HCID 6344Dichloromethane溶媒HCID 23212559water MeOtBu溶媒

実験手順

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.

後処理

  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]

出典と根拠

ORDレコード
ord-51124c6f60614eacb08edd621d6248dc
出典データセット
uspto-grants-2016_07
特許番号
US09382272B2

反応ノート

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