Lithium hydroxide, monohydrate → methyl 7-[(1R,2R,3R,5S)-5-acetoxy-2-((E)-4,4-difluoro-3-oxo-4-phenyl-1-butenyl)-3-(2-tetrahydropyranyloxy)cyclopentyl]heptanate

HRID 1874105Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1874105
[F:1][C:2]([F:18])([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:3](=[O:11])[CH2:4]P(=O)(OC)OC.O.[OH-].[Li+].[C:22]([O:25][C@@H:26]1[C@H:30]([CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][C:37]([O:39][CH3:40])=[O:38])[C@@H:29]([CH:41]=O)[C@H:28]([O:43][CH:44]2[CH2:49][CH2:48][CH2:47][CH2:46][O:45]2)[CH2:27]1)(=[O:24])[CH3:23]>COC(C)(C)C.O>[C:22]([O:25][C@@H:26]1[C@H:30]([CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][C:37]([O:39][CH3:40])=[O:38])[C@@H:29](/[CH:41]=[CH:4]/[C:3](=[O:11])[C:2]([F:1])([F:18])[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[C@H:28]([O:43][CH:44]2[CH2:49][CH2:48][CH2:47][CH2:46][O:45]2)[CH2:27]1)(=[O:24])[CH3:23]

Komponenten

6

Edukt 3

HCID 168937Lithium hydroxide, monohydrateHCID 11729034methyl 7-[(1R,2R,3R,5S)-5-acetoxy-2-formyl-3-(2-tetrahydropyranyl-oxy)cyclopentyl]heptanateHCID 21949543Dimethyl (3,3-difluoro-2-oxo-3-phenylpropyl)phosphonate

Produkt 1

HCID 59514701methyl 7-[(1R,2R,3R,5S)-5-acetoxy-2-((E)-4,4-difluoro-3-oxo-4-phenyl-1-butenyl)-3-(2-tetrahydropyranyloxy)cyclopentyl]heptanateAusbeute 74,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittel2×HCID 15413tert-Butyl methyl etherLösungsmittel2×

Versuchsvorschrift

To a solution of dimethyl (3,3-difluoro-2-oxo-3-phenylpropyl)phosphonate (6) (0.262 g, 0.942 mmol) in t-butyl methyl ether (7 ml), lithium hydroxide monohydrate (38.2 mg, 0.910 mmol) was added and the mixture was stirred for one hour at room temperature. A solution of methyl 7-[(1R,2R,3R,5S)-5-acetoxy-2-formyl-3-(2-tetrahydropyranyloxy)cyclopentyl]heptanate (2) (0.250 g, 0.627 mmol) in t-butyl methyl ether (3 ml) and water (0.3 ml) were added thereto, and the mixed solution was heat refluxed for approximately 48 hours. After cooling to room temperature, the reaction mixture was added to water, and extracted twice with t-butyl methyl ether. The organic layers were combined, sequentially washed with water, saturated sodium bicarbonate water and saturated aqueous sodium chloride, and then dried with anhydrous magnesium sulfate. After concentration under reduced pressure, the residue was purified by silica gel column chromatography (Merck Art. 9385: 200 g; ethyl acetate:hexane=2:3). The fractions containing impurities were re-purified by silica gel column chromatography (Merck Art. 9385: 120 g; ethyl acetate:hexane=2:3), to give methyl 7-[(1R,2R,3R,5S)-5-acetoxy-2-((E)-4,4-difluoro-3-oxo-4-phenyl-1-butenyl)-3-(2-tetrahydropyranyloxy)cyclopentyl]heptanate (7) (0.257 g; 0.467 mmol; yield: 74.4%) as a colorless oil.

Aufarbeitung

  1. temperaturethe mixed solution was heat
  2. temperaturerefluxed for approximately 48 hours
  3. temperatureAfter cooling to room temperature
  4. extractionextracted twice with t-butyl methyl ether
  5. washsequentially washed with water, saturated sodium bicarbonate water and saturated aqueous sodium chloride
  6. dry with materialdried with anhydrous magnesium sulfate
  7. concentrationAfter concentration under reduced pressure
  8. customthe residue was purified by silica gel column chromatography (Merck Art. 9385: 200 g; ethyl acetate:hexane=2:3)
  9. additionThe fractions containing impurities
  10. customwere re-purified by silica gel column chromatography (Merck Art. 9385: 120 g; ethyl acetate:hexane=2:3)

Quellen und Nachweise

ORD-Eintrag
ord-0c90aa4d61e04f45839c93387300f38d
Quelldatensatz
uspto-grants-2012_11
Patentnummer
US08304562B2

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