Ethyl Acetate → HCID 66645611, compound

HRID 1694911Notes

Reaction equation

HRID 1694911 reaction equation
C(=O)(O)[O-].[Na+].[CH2:6]([O:13][C:14](Cl)=[O:15])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[NH2:17][C@H:18]([C@@H:39]1[CH2:43][C@@H:42]([CH:44]([CH3:46])[CH3:45])[C:41](=[O:47])[O:40]1)[CH2:19][N:20]1[C:25]([CH3:27])([CH3:26])[CH2:24][N:23]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[O:34][CH2:35][O:36][CH3:37])[C:22](=[O:38])[CH2:21]1.C(OCC)(=O)C>[Cl-].[Na+].O.O>[CH2:6]([O:13][C:14](=[O:15])[NH:17][C@H:18]([C@@H:39]1[CH2:43][C@@H:42]([CH:44]([CH3:45])[CH3:46])[C:41](=[O:47])[O:40]1)[CH2:19][N:20]1[CH2:21][C:22](=[O:38])[N:23]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[O:34][CH2:35][O:36][CH3:37])[CH2:24][C:25]1([CH3:27])[CH3:26])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 10387Benzyl chloroformateHCID 516892Sodium BicarbonateHCID 666458194-{(S)-2-amino-2-[(2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl]ethyl}1-(2-methoxymethoxyphenyl)-5,5-dimethylpiperazin-2-one

Product 1

HCID 66645611HCID 66645611, compoundYield 96.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 57417360Sodium chloride; waterSolvent2×

Procedure

206 mg of cesium carbonate (0.63 mmol) was added to a solution of 326 mg of N-{(S)-1-[(2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl]-2-[4-(2-methoxymethoxyphenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]ethyl}-2-nitrobenzenesulfonamide obtained in the above reaction (0.53 mmol) and 0.12 ml of thiophenol (content: 95%) (1.1 mmol) in N,N-dimethylformamide (5 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). 49 mg of sodium bicarbonate (0.57 mmol) and 78 μl of benzyloxycarbonyl chloride (0.53 mmol) were added to a solution of 209 mg of 4-{(S)-2-amino-2-[(2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl]ethyl}1-(2-methoxymethoxyphenyl)-5,5-dimethylpiperazin-2-one obtained above (0.48 mmol) in a mixed solvent of ethyl acetate (3 ml) and water (3 ml) under ice-cooling, and the mixture was stirred at the same temperature for 30 minutes. Brine was added to the reaction mixture, followed by extraction with ethyl acetate. Then, the organic layer was dried over anhydrous sodium sulfate. After filtration, the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (elution solvent:methylene chloride/methanol=20/1) to obtain 263 mg of {(S)-1-[(2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl]-2-[4-(2-methoxymethoxyphenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]ethyl}carbamic acid benzyl ester (yield: 87%).

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. temperaturecooling
  7. stirringthe mixture was stirred at the same temperature for 30 minutes
  8. extractionfollowed by extraction with ethyl acetate
  9. dry with materialThen, the organic layer was dried over anhydrous sodium sulfate
  10. filtrationAfter filtration
  11. customthe solvent was evaporated under reduced pressure
  12. customThe residue was purified by silica gel column chromatography (elution solvent:methylene chloride/methanol=20/1)

Sources & evidence

ORD record
ord-b22fc30768254cc88475a8deec3ce35a
Source dataset
uspto-grants-2012_04
Patent number
US08158790B2

Reaction notes

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