Dichloromethane → (2R)-2-[(2S)-3-(Benzoylthio)-2-methylpropionylamino]-3-(4-methylbenzylthio)propionic acid

HRID 1003651Notes

Reaction equation

HRID 1003651 reaction equation
C(N(CC)CC)C.[CH3:8][C:9]1[CH:22]=[CH:21][C:12]([CH2:13][S:14][CH2:15][C@@H:16]([C:18]([OH:20])=[O:19])[NH2:17])=[CH:11][CH:10]=1.C(Cl)Cl.[C:26]([S:34][CH2:35][C@@H:36]([CH3:49])[C:37](OC1C=CC([N+]([O-])=O)=CC=1)=[O:38])(=[O:33])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>CN(C)C=O>[C:26]([S:34][CH2:35][C@@H:36]([CH3:49])[C:37]([NH:17][C@@H:16]([CH2:15][S:14][CH2:13][C:12]1[CH:11]=[CH:10][C:9]([CH3:8])=[CH:22][CH:21]=1)[C:18]([OH:20])=[O:19])=[O:38])(=[O:33])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 13994756S-p-Methylbenzyl-L-cysteineHCID 154536594-Nitrophenyl (2S)-3-benzoylthio-2-methylpropionate

Product 1

HCID 15453679(2R)-2-[(2S)-3-(Benzoylthio)-2-methylpropionylamino]-3-(4-methylbenzylthio)propionic acidYield 68.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Triethylamine (0.464 ml) is added to a solution of S-(4-methylbenzyl)-L-cysteine (reference compound No. 2-1, 500 mg) in a mixed solvent of methylene chloride (20 ml)/dimethylformamide (5 ml) under ice-cooling, and the mixture is stirred. 4-Nitrophenyl (2S)-3-benzoylthio-2-methylpropionate (reference compound No. 1-1, 919 mg) is added to the system of reaction, and the system is stirred overnight. The system of reaction is further stirred overnight at 40° to 50° C. After the reaction is completed, the mixture is concentrated under reduced pressure, a 10%, aqueous citric acid solution is added to the residue, and the whole is extracted with ethyl acetate. The organic layer is washed with water and a saturated sodium chloride solution successively, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue is purified by silica gel column chromatography to give 660 mg (68.9%) of the titled compound. (Compound No. 1-1)

Workup

  1. temperaturecooling
  2. stirringthe system is stirred overnight
  3. customThe system of reaction
  4. stirringis further stirred overnight at 40° to 50° C
  5. concentrationthe mixture is concentrated under reduced pressure
  6. additiona 10%, aqueous citric acid solution is added to the residue
  7. extractionthe whole is extracted with ethyl acetate
  8. washThe organic layer is washed with water
  9. dry with materiala saturated sodium chloride solution successively, dried over anhydrous sodium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customThe obtained residue is purified by silica gel column chromatography

Sources & evidence

ORD record
ord-e19f5ff67c3f446f8bf5238fe557bb84
Source dataset
uspto-grants-2000_04
Patent number
US06046235

Reaction notes

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