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

HRID 1695002Notes

Reaction equation

HRID 1695002 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:7][C:8]1([CH3:45])[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:32]S(C1C=CC=CC=1[N+]([O-])=O)(=O)=O)[C@@H:24]1[CH2:28][C@@H:27]([CH2:29][CH3:30])[C:26](=[O:31])[O:25]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=2C)C(=O)C1>C(#N)C.[Cl-].[Na+].O.C(OCC)(=O)C.O>[C:61]([O:60][C:58](=[O:59])[NH:32][C@H:23]([C@@H:24]1[CH2:28][C@@H:27]([CH2:29][CH3:30])[C:26](=[O:31])[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([CH3:45])[CH3:7])([CH3:64])([CH3:63])[CH3:62]

Participants

11

Reactant 6

HCID 7969ThiophenolHCID 10796Cesium carbonateHCID 90495Di-tert-butyl dicarbonateHCID 516892Sodium BicarbonateHCID 666455704-{(S)-2-amino-2-[(2S,4R)-4-ethyl-5-oxotetrahydrofuran-2-yl]ethyl}-5,5-dimethyl-1-(2-methylphenyl)piperazin-2-oneHCID 66645655N-{(S)-2-[2,2-Dimethyl-4-(2-methylphenyl)-5-oxopiperazin-1-yl]-1-[(2S,4R)-4-ethyl-5-oxotetrahydrofuran-2-yl]ethyl}-2-nitrobenzenesulfonamide

Product 1

HCID 66645525{(S)-2-[2,2-Dimethyl-4-(2-methylphenyl)-5-oxopiperazin-1-yl]-1-[(2S,4R)-4-ethyl-5-oxotetrahydrofuran-2-yl]ethyl}carbamic acid t-butyl esterYield 88.6%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent2×

Procedure

854 mg of cesium carbonate (2.62 mmol) was added to a solution of 1.22 g of N-{(S)-2-[2,2-dimethyl-4-(2-methylphenyl)-5-oxopiperazin-1-yl]-1-[(2S,4R)-4-ethyl-5-oxotetrahydrofuran-2-yl]ethyl}-2-nitrobenzenesulfonamide obtained in Example (110a) (2.18 mmol) and 0.45 ml of thiophenol (content: 95%) (4.37 mmol) in acetonitrile (22 ml) under a nitrogen atmosphere at room temperature, and the mixture was stirred at the same temperature for one hour. 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=19/1-9/1). 197 mg of sodium bicarbonate (2.34 mmol) and 510 mg of di-t-butyl dicarbonate (2.34 mmol) were added to a solution of 4-{(S)-2-amino-2-[(2S,4R)-4-ethyl-5-oxotetrahydrofuran-2-yl]ethyl}-5,5-dimethyl-1-(2-methylphenyl)piperazin-2-one obtained above in ethyl acetate (10 ml)-water (10 ml), and the mixture was stirred at room temperature for 15 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:n-hexane/ethyl acetate=3/7) to obtain 915 mg of the title compound (yield: 88%).

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=19/1-9/1)
  6. stirringthe mixture was stirred at room temperature for 15 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:n-hexane/ethyl acetate=3/7)

Sources & evidence

ORD record
ord-2bd09c7e1cab4e4f94e2ec25cf8ea291
Source dataset
uspto-grants-2012_04
Patent number
US08158790B2

Reaction notes

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