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

HRID 1694996Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1694996
C(=O)([O-])[O-].[Cs+].[Cs+].[Cl:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[N:14]1[C:19](=[O:20])[CH2:18][N:17]([CH2:21][C@H:22]([NH:31]S(C2C=CC=CC=2[N+]([O-])=O)(=O)=O)[C@@H:23]2[CH2:27][C@@H:26]([CH2:28][CH3:29])[C:25](=[O:30])[O:24]2)[C:16]([CH3:45])([CH3:44])[CH2:15]1.C1(S)C=CC=CC=1.C(=O)(O)[O-].[Na+].[C:58](OC(OC(C)(C)C)=O)([O:60][C:61]([CH3:64])([CH3:63])[CH3:62])=[O:59].N[C@H]([C@@H]1C[C@@H](CC)C(=O)O1)CN1C(C)(C)CN(C2C=CC=CC=2Cl)C(=O)C1>CN(C)C=O.[Cl-].[Na+].O.C(OCC)(=O)C.O>[C:61]([O:60][C:58](=[O:59])[NH:31][C@H:22]([C@@H:23]1[CH2:27][C@@H:26]([CH2:28][CH3:29])[C:25](=[O:30])[O:24]1)[CH2:21][N:17]1[CH2:18][C:19](=[O:20])[N:14]([C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[Cl:7])[CH2:15][C:16]1([CH3:45])[CH3:44])([CH3:64])([CH3:63])[CH3:62]

Komponenten

11

Edukt 6

HCID 7969ThiophenolHCID 10796Cesium carbonateHCID 90495Di-tert-butyl dicarbonateHCID 516892Sodium BicarbonateHCID 66645496N-{(S)-2-[4-(2-Chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-1-[(2S,4R)-4-ethyl-5-oxotetrahydrofuran-2-yl]ethyl}-2-nitrobenzenesulfonamideHCID 666459604-{(S)-2-amino-2-[(2S,4R)-4-ethyl-5-oxotetrahydrofuran-2-yl]ethyl}-1-(2-chlorophenyl)-5,5-dimethylpiperazin-2-one

Produkt 1

HCID 66645434{(S)-2-[4-(2-Chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-1-[(2S,4R)-4-ethyl-5-oxotetrahydrofuran-2-yl]ethyl}carbamic acid t-butyl esterAusbeute 88 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 57417360Sodium chloride; waterLösungsmittel2×

Versuchsvorschrift

1.00 g of cesium carbonate (3.08 mmol) was added to a solution of 1.49 g of N—{(S)-2-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-1-[(2S,4R)-4-ethyl-5-oxotetrahydrofuran-2-yl]ethyl}-2-nitrobenzenesulfonamide obtained in Example (106h) (2.57 mmol) and 0.52 ml of thiophenol (content: 95%) (5.14 mmol) in N,N-dimethylformamide (13 ml) under a nitrogen atmosphere at room temperature, and the mixture was stirred at the same temperature for 1.5 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=50/1-10/1). 235 mg of sodium bicarbonate (2.80 mmol) and 610 mg of di-t-butyl dicarbonate (2.80 mmol) were added to a solution of 4-{(S)-2-amino-2-[(2S,4R)-4-ethyl-5-oxotetrahydrofuran-2-yl]ethyl}-1-(2-chlorophenyl)-5,5-dimethylpiperazin-2-one obtained above in ethyl acetate (12 ml)-water (12 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=2/1-1/1) to obtain 1.11 g of the title compound (yield: 88%).

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=50/1-10/1)
  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=2/1-1/1)

Quellen und Nachweise

ORD-Eintrag
ord-25c1e5c9c8604731934fd78f791eb34a
Quelldatensatz
uspto-grants-2012_04
Patentnummer
US08158790B2

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