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

HRID 1694894Notes

Reaction equation

HRID 1694894 reaction equation
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:32]S(C2C=CC=CC=2[N+]([O-])=O)(=O)=O)[C@@H:23]2[CH2:27][C@@H:26]([CH:28]([CH3:30])[CH3:29])[C:25](=[O:31])[O:24]2)[C:16]([CH3:46])([CH3:45])[CH2:15]1.C1(S)C=CC=CC=1.C(N(CC)CC)C.[C:61](OC(OC(C)(C)C)=O)([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62].N[C@H]([C@@H]1C[C@@H](C(C)C)C(=O)O1)CN1C(C)(C)CN(C2C=CC=CC=2Cl)C(=O)C1>CN(C)C=O.[Cl-].[Na+].O.C(Cl)Cl>[C:64]([O:63][C:61](=[O:62])[NH:32][C@H:22]([C@@H:23]1[CH2:27][C@@H:26]([CH:28]([CH3:29])[CH3:30])[C:25](=[O:31])[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([CH3:46])[CH3:45])([CH3:67])([CH3:66])[CH3:65]

Participants

10

Reactant 6

HCID 7969ThiophenolHCID 8471TriethylamineHCID 10796Cesium carbonateHCID 90495Di-tert-butyl dicarbonateHCID 66645367N-{(S)-2-[4-(2-Chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-1-[(2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl]ethyl}-2-nitrobenzenesulfonamideHCID 666457214-{(S)-2-amino-2-[(2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl]ethyl}1-(2-chlorophenyl)-5,5-dimethylpiperazin-2-one

Product 1

HCID 66645421{(S)-2-[4-(2-Chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-1-[(2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl]ethyl}carbamic acid t-butyl esterYield 80.7%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 57417360Sodium chloride; waterSolvent2×

Procedure

197 mg of cesium carbonate (0.61 mmol) was added to a solution of 299 mg of N-{(S)-2-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-1-[(2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl]ethyl}-2-nitrobenzenesulfonamide obtained in Example (1l) (0.50 mmol) and 0.11 ml of thiophenol (content: 95%) (1.00 mmol) in N,N-dimethylformamide (5 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=20/1-10/1). 0.21 ml of triethylamine (1.51 mmol) and 132 mg of di-t-butyl dicarbonate (0.61 mmol) were added to a solution of the resulting 4-{(S)-2-amino-2-[(2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl]ethyl}1-(2-chlorophenyl)-5,5-dimethylpiperazin-2-one in methylene chloride (5 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:methylene chloride/ethyl acetate=2/1) to obtain 205 mg of the title compound (yield: 80%).

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 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:methylene chloride/ethyl acetate=2/1)

Sources & evidence

ORD record
ord-0a559a37ef8e4f72b2c57250ed496c11
Source dataset
uspto-grants-2012_04
Patent number
US08158790B2

Reaction notes

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