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

HRID 1003652Notes

Reaction equation

HRID 1003652 reaction equation
Cl.[O:2]1[CH2:7][CH2:6]OCC1.[CH3:8][NH:9][C:10](=[O:30])[C@@H:11]([NH:22][C:23]([O:25]C(C)(C)C)=O)[CH2:12][S:13][CH2:14][C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=1>>[CH3:8][NH:9][C:10](=[O:30])[C@@H:11]([NH:22][C:23](=[O:25])[C@H:11]([CH3:10])[CH2:12][S:13][C:7](=[O:2])[C:6]1[CH:19]=[CH:20][CH:15]=[CH:16][CH:17]=1)[CH2:12][S:13][CH2:14][C:15]1[CH:16]=[CH:17][C:18]([CH3:21])=[CH:19][CH:20]=1

Participants

3

Reactant 2

HCID 15453678(2R)-2-(tert-Butoxycarbonylamino)-3-(4-methylbenzylthio)propionic acid methylamideHCID 204431481,4-Dioxane hydrochloride

Product 1

HCID 54442773(2R)-2-[(2S)-3-(Benzoylthio)-2-methylpropionylamino]-3-(4-methylbenzylthio)propionic acid methylamide

Procedure

4 N hydrogen chloride/dioxane (1.5 ml) is added to (2R)-2-(tert-butoxycarbonylamino)-3-(4-methylbenzylthio)propionic acid methylamide (reference compound No. 4-1, 200 mg), and the mixture is stirred at room temperature for one hour. The reaction mixture is concentrated under reduced pressure, and the obtained residue is dissolved in methylene chloride (5 ml). To the solution are added N-methylmorpholine (0.119 ml), 1-hydroxybenzotriazole (109 mg), (2S)-3-(benzoylthio)-2-methylpropionic acid (182 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (135 mg) and N-methylmorpholine (0.077 ml) successively under ice-cooling, and the mixture is stirred overnight at room temperature. A 5% aqueous sodium hydrogencarbonate solution is added to the system of reaction, and the whole is extracted with ethyl acetate. The organic layer is washed with a 5% aqueous sodium hydrogencarbonate solution and a saturated sodium chloride solution successively, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue is purified by silica gel column chromatography to give the titled compound.

Workup

  1. concentrationThe reaction mixture is concentrated under reduced pressure
  2. dissolutionthe obtained residue is dissolved in methylene chloride (5 ml)
  3. additionTo the solution are added N-methylmorpholine (0.119 ml), 1-hydroxybenzotriazole (109 mg), (2S)-3-(benzoylthio)-2-methylpropionic acid (182 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (135 mg) and N-methylmorpholine (0.077 ml) successively under ice-
  4. temperaturecooling
  5. stirringthe mixture is stirred overnight at room temperature
  6. additionA 5% aqueous sodium hydrogencarbonate solution is added to the system of reaction
  7. extractionthe whole is extracted with ethyl acetate
  8. washThe organic layer is washed with a 5% aqueous sodium hydrogencarbonate solution
  9. dry with materiala saturated sodium chloride solution successively, dried over magnesium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customThe obtained residue is purified by silica gel column chromatography

Sources & evidence

ORD record
ord-7de3373dbcf943cc90802582b38edd63
Source dataset
uspto-grants-2000_04
Patent number
US06046235

Reaction notes

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