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

HRID 1694946Notes

Reaction equation

HRID 1694946 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:7][C:8]1([CH3:47])[CH2:13][N:12]([C:14]2[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=2[CH3:21])[C:11](=[O:22])[CH2:10][N:9]1[CH2:23][C@H:24]([NH:34]S(C1C=CC=CC=1[N+]([O-])=O)(=O)=O)[C@@H:25]1[CH2:29][C@@H:28]([CH:30]([CH3:32])[CH3:31])[C:27](=[O:33])[O:26]1.C1(S)C=CC=CC=1.C(=O)(O)[O-].[Na+].[C:60](OC(OC(C)(C)C)=O)([O:62][C:63]([CH3:66])([CH3:65])[CH3:64])=[O:61].N[C@H]([C@@H]1C[C@@H](C(C)C)C(=O)O1)CN1C(C)(C)CN(C2C=C(F)C=CC=2C)C(=O)C1>[Cl-].[Na+].O.C(OCC)(=O)C.O>[C:63]([O:62][C:60](=[O:61])[NH:34][C@H:24]([C@@H:25]1[CH2:29][C@@H:28]([CH:30]([CH3:32])[CH3:31])[C:27](=[O:33])[O:26]1)[CH2:23][N:9]1[CH2:10][C:11](=[O:22])[N:12]([C:14]2[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=2[CH3:21])[CH2:13][C:8]1([CH3:47])[CH3:7])([CH3:66])([CH3:65])[CH3:64]

Participants

10

Reactant 6

HCID 7969ThiophenolHCID 10796Cesium carbonateHCID 90495Di-tert-butyl dicarbonateHCID 516892Sodium BicarbonateHCID 66645703N-{(S)-2-[2,2-Dimethyl-4-(5-fluoro-2-methylphenyl)-5-oxopiperazin-1-yl]-1-[(2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl]ethyl}-2-nitrobenzenesulfonamideHCID 666459814-{(S)-2-amino-2-[(2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl]ethyl}-5,5-dimethyl-1-(5-fluoro-2-methylphenyl)piperazin-2-one

Product 1

HCID 66645725{(S)-2-[2,2-Dimethyl-4-(5-fluoro-2-methylphenyl)-5-oxopiperazin-1-yl]-1-[(2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl]ethyl}carbamic acid t-butyl esterYield 93%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent2×

Procedure

953 mg of cesium carbonate (2.92 mmol) was added to a solution of 1.44 g of N-{(S)-2-[2,2-dimethyl-4-(5-fluoro-2-methylphenyl)-5-oxopiperazin-1-yl]-1-[(2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl]ethyl}-2-nitrobenzenesulfonamide obtained in Example (70e) (2.43 mmol) and 0.52 ml of thiophenol (content: 95%) (4.87 mmol) in acetolitrile (25 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). 211 mg of sodium bicarbonate (2.51 mmol) and 549 mg of di-t-butyl dicarbonate (2.51 mmol) were added to a solution of 4-{(S)-2-amino-2-[(2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl]ethyl}-5,5-dimethyl-1-(5-fluoro-2-methylphenyl)piperazin-2-one obtained above in a mixture of ethyl acetate (11 ml) and water (11 ml), and the mixture was stirred at room temperature for four 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/ethyl acetate=5/1-3/1) to obtain 996 mg of the title compound (yield: 93%).

Workup

  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 four hours
  7. extractionfollowed by extraction with methylene chloride
  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=5/1-3/1)

Sources & evidence

ORD record
ord-b36327a7631042a583f5bd114348350d
Source dataset
uspto-grants-2012_04
Patent number
US08158790B2

Reaction notes

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