Thiophenol → {(S)-2-[2,2-Dimethyl-4-(2-methylphenyl)-5-oxopiperazin-1-yl]-1-[(2S,4R)-4-methyl-5-oxotetrahydrofuran-2-yl]ethyl}carbamic acid t-butyl ester

HRID 1694964Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1694964
C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:7][C:8]1([CH3:44])[CH2:13][N:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[CH3:20])[C:11](=[O:21])[CH2:10][N:9]1[CH2:22][C@H:23]([NH:31]S(C1C=CC=CC=1[N+]([O-])=O)(=O)=O)[C@@H:24]1[CH2:28][C@@H:27]([CH3:29])[C:26](=[O:30])[O:25]1.C1(S)C=CC=CC=1.C(=O)(O)[O-].[Na+].[C:57](OC(OC(C)(C)C)=O)([O:59][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:58].N[C@H]([C@@H]1C[C@@H](C)C(=O)O1)CN1C(C)(C)CN(C2C=CC=CC=2C)C(=O)C1>C(#N)C.[Cl-].[Na+].O.C(OCC)(=O)C.O>[C:60]([O:59][C:57](=[O:58])[NH:31][C@H:23]([C@@H:24]1[CH2:28][C@@H:27]([CH3:29])[C:26](=[O:30])[O:25]1)[CH2:22][N:9]1[CH2:10][C:11](=[O:21])[N:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[CH3:20])[CH2:13][C:8]1([CH3:7])[CH3:44])([CH3:63])([CH3:62])[CH3:61]

Komponenten

11

Edukt 6

HCID 7969ThiophenolHCID 10796Cesium carbonateHCID 90495Di-tert-butyl dicarbonateHCID 516892Sodium BicarbonateHCID 66645414N-{(S)-2-[2,2-Dimethyl-4-(2-methylphenyl)-5-oxopiperazin-1-yl]-1-[(2S,4R)-4-methyl-5-oxotetrahydrofuran-2-yl]ethyl}-2-nitrobenzenesulfonamideHCID 666459334-{(S)-2-amino-2-[(2S,4R)-4-methyl-5-oxotetrahydrofuran-2-yl]ethyl}-5,5-dimethyl-1-(2-methylphenyl)piperazin-2-one

Produkt 1

HCID 66645428{(S)-2-[2,2-Dimethyl-4-(2-methylphenyl)-5-oxopiperazin-1-yl]-1-[(2S,4R)-4-methyl-5-oxotetrahydrofuran-2-yl]ethyl}carbamic acid t-butyl esterAusbeute 62 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 962WaterLösungsmittelHCID 6342AcetonitrileLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 57417360Sodium chloride; waterLösungsmittel2×

Versuchsvorschrift

704 mg of cesium carbonate (2.16 mmol) was added to a solution of 980 mg of N-{(S)-2-[2,2-dimethyl-4-(2-methylphenyl)-5-oxopiperazin-1-yl]-1-[(2S,4R)-4-methyl-5-oxotetrahydrofuran-2-yl]ethyl}-2-nitrobenzenesulfonamide obtained in Example (85a) (1.8 mmol) and 0.55 ml of thiophenol (content: 95%) (5.4 mmol) in acetonitrile (18 ml) under a nitrogen atmosphere at room temperature, and the mixture was stirred at the same temperature for two hours. Brine was added to the reaction mixture, followed by extraction with methylene chloride. Then, the organic layer was dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (elution solvent:methylene chloride/methanol=20/1-10/1). 160 mg of sodium bicarbonate (1.9 mmol) and 416 mg of di-t-butyl dicarbonate (1.9 mmol) were added to a solution of 4-{(S)-2-amino-2-[(2S,4R)-4-methyl-5-oxotetrahydrofuran-2-yl]ethyl}-5,5-dimethyl-1-(2-methylphenyl)piperazin-2-one obtained above in ethyl acetate (7 ml)-water (7 ml), and the mixture was stirred at room temperature for 2.5 hours. Brine was added to the reaction mixture, followed by extraction with ethyl acetate. Then, the organic layer was dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (elution solvent:methylene chloride/ethyl acetate=2/1) to obtain 506 mg of the title compound (yield: 62%).

Aufarbeitung

  1. extractionfollowed by extraction with methylene chloride
  2. dry with materialThen, the organic layer was dried over anhydrous magnesium sulfate
  3. filtrationAfter filtration
  4. customthe solvent was evaporated under reduced pressure
  5. customthe residue was purified by silica gel column chromatography (elution solvent:methylene chloride/methanol=20/1-10/1)
  6. stirringthe mixture was stirred at room temperature for 2.5 hours
  7. extractionfollowed by extraction with ethyl acetate
  8. dry with materialThen, the organic layer was dried over anhydrous magnesium sulfate
  9. filtrationAfter filtration
  10. customthe solvent was evaporated under reduced pressure
  11. customthe residue was purified by silica gel column chromatography (elution solvent:methylene chloride/ethyl acetate=2/1)

Quellen und Nachweise

ORD-Eintrag
ord-d581d7d8ce9948deaa5cc8b777ad3b75
Quelldatensatz
uspto-grants-2012_04
Patentnummer
US08158790B2

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