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

HRID 1694976Notes

Reaction equation

HRID 1694976 reaction equation
[C:1](=[O:4])([O-:3])[O-].[Cs+].[Cs+].[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([F:14])=[CH:10][C:9]=1[N:15]1[C:20](=[O:21])[CH2:19][N:18]([CH2:22][C@H:23]([NH:31]S(C2C=CC=CC=2[N+]([O-])=O)(=O)=O)[C@@H:24]2[CH2:28][C@@H:27](C)[C:26](=O)O2)[C:17]([CH3:45])([CH3:44])[CH2:16]1.C1(S)C=CC=CC=1.C(=O)(O)[O-].[Na+].C(O[C:66]([O:68][C:69]([CH3:72])([CH3:71])[CH3:70])=[O:67])(OC(C)(C)C)=O.N[C@H]([C@@H]1C[C@@H](C)C(=O)O1)CN1C(C)(C)CN(C2C=C(F)C=CC=2Cl)C(=O)C1>C(#N)C.[Cl-].[Na+].O.C(OCC)(=O)C.O>[C:69]([O:68][C:66](=[O:67])[NH:31][C@H:23]([C@@H:24]1[CH2:28][C@@H:27]([CH3:26])[C:1](=[O:4])[O:3]1)[CH2:22][N:18]1[CH2:19][C:20](=[O:21])[N:15]([C:9]2[CH:10]=[C:11]([F:14])[CH:12]=[CH:13][C:8]=2[Cl:7])[CH2:16][C:17]1([CH3:44])[CH3:45])([CH3:70])([CH3:71])[CH3:72]

Participants

11

Reactant 6

HCID 7969ThiophenolHCID 10796Cesium carbonateHCID 90495Di-tert-butyl dicarbonateHCID 516892Sodium BicarbonateHCID 66645536N-{(S)-2-[4-(2-Chloro-5-fluorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-1-[(2S,4R)-4-methyl-5-oxotetrahydrofuran-2-yl]ethyl}-2-nitrobenzenesulfonamideHCID 666457264-{(S)-2-amino-2-[(2S,4R)-4-methyl-5-oxotetrahydrofuran-2-yl]ethyl}1-(2-chloro-5-fluorophenyl)-5,5-dimethylpiperazin-2-one

Product 1

HCID 66645673{(S)-2-[4-(2-Chloro-5-fluorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-1-[(2S,4R)-4-methyl-5-oxotetrahydrofuran-2-yl]ethyl}carbamic acid t-butyl esterYield 80.2%

Reagents, catalysts & solvents 4

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

Procedure

893 mg of cesium carbonate (2.53 mmol) was added to a solution of 1.23 g of N-{(S)-2-[4-(2-chloro-5-fluorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-1-[(2S,4R)-4-methyl-5-oxotetrahydrofuran-2-yl]ethyl}-2-nitrobenzenesulfonamide obtained in Example (97a) (2.11 mmol) and 0.45 ml of thiophenol (content: 95%) (4.22 mmol) in acetonitrile (10 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). 176 mg of sodium bicarbonate (2.09 mmol) and 456 mg of di-t-butyl dicarbonate (2.09 mmol) were added to a solution of 4-{(S)-2-amino-2-[(2S,4R)-4-methyl-5-oxotetrahydrofuran-2-yl]ethyl}1-(2-chloro-5-fluorophenyl)-5,5-dimethylpiperazin-2-one obtained above in ethyl acetate (10 ml)-water (10 ml), and the mixture was stirred at room temperature for two 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 835 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 two 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)

Sources & evidence

ORD record
ord-567db9a7b1d84297ae5f1be5a5114a20
Source dataset
uspto-grants-2012_04
Patent number
US08158790B2

Reaction notes

Loading…