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

HRID 1694934
Notes
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Reaction equation

HRID 1694934 reaction equation
C(=O)([O-])[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:33]S(C2C=CC=CC=2[N+]([O-])=O)(=O)=O)[C@@H:24]2[CH2:28][C@@H:27]([CH:29]([CH3:31])[CH3:30])[C:26](=[O:32])[O:25]2)[C:17]([CH3:47])([CH3:46])[CH2:16]1.C1(S)C=CC=CC=1.C(N(CC)CC)C.[C:62](OC(OC(C)(C)C)=O)([O:64][C:65]([CH3:68])([CH3:67])[CH3:66])=[O:63].N[C@H]([C@@H]1C[C@@H](C(C)C)C(=O)O1)CN1C(C)(C)CN(C2C=C(F)C=CC=2Cl)C(=O)C1>CN(C)C=O.[Cl-].[Na+].O.C(Cl)Cl>[C:65]([O:64][C:62](=[O:63])[NH:33][C@H:23]([C@@H:24]1[CH2:28][C@@H:27]([CH:29]([CH3:30])[CH3:31])[C:26](=[O:32])[O:25]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([CH3:47])[CH3:46])([CH3:68])([CH3:67])[CH3:66]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

10

Reactant 6

HCID 7969ThiophenolHCID 8471TriethylamineHCID 10796Cesium carbonateHCID 90495Di-tert-butyl dicarbonateHCID 666454914-{(S)-2-amino-2-[(2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl]ethyl}-1-(2-chloro-5-fluorophenyl)-5,5-dimethylpiperazin-2-one
HCID 66645783
N-{(S)-2-[4-(2-Chloro-5-fluorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-1-[(2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl]ethyl}-2-nitrobenzenesulfonamide

Product 1

HCID 66645857{(S)-2-[4-(2-Chloro-5-fluorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-1-[(2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl]ethyl}carbamic acid t-butyl esterYield 70.3%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 57417360Sodium chloride; waterSolvent2×

Procedure

1.1 g of cesium carbonate (3.42 mmol) was added to a solution of 1.70 g of N-{(S)-2-[4-(2-chloro-5-fluorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-1-[(2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl]ethyl}-2-nitrobenzenesulfonamide obtained in Example (62e) (2.85 mmol) and 0.87 ml of thiophenol (content: 95%) (8.54 mmol) in N,N-dimethylformamide (15 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). 0.99 ml of triethylamine (7.11 mmol) and 620 mg of di-t-butyl dicarbonate (2.84 mmol) were added to a solution of 4-{(S)-2-amino-2-[(2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl]ethyl}-1-(2-chloro-5-fluorophenyl)-5,5-dimethylpiperazin-2-one obtained above in methylene chloride (24 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=3/1) to obtain 1.05 g of the title compound (yield: 70%).

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=3/1)

Sources & evidence

ORD record
ord-1fee5ce7e8b442c9b6dd1fe6d2389729
Source dataset
uspto-grants-2012_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08158790B2

Reaction notes

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