1-tert-butylcarbonylmethyl-2-oxo-3-[(2S)-(2-tert-butoxycarbonylamino-3-phenylpropionyl)amino]-5-phenyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine → (-)-1-tert-butylcarbonylmethyl-2-oxo-3-[(2S)-(2-amino-3-phenylpropionyl)amino]-5-phenyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine

HRID 1979369Notes

Reaction equation

HRID 1979369 reaction equation
[C:1]([C:5]([CH2:7][N:8]1[C:14]2[CH:15]=[C:16]([CH3:19])[CH:17]=[CH:18][C:13]=2[N:12]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:11][CH:10]([NH:26][C:27](=[O:44])[C@@H:28]([NH:36]C(OC(C)(C)C)=O)[CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:9]1=[O:45])=[O:6])([CH3:4])([CH3:3])[CH3:2]>Cl.O1CCOCC1>[C:1]([C:5]([CH2:7][N:8]1[C:14]2[CH:15]=[C:16]([CH3:19])[CH:17]=[CH:18][C:13]=2[N:12]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:11][CH:10]([NH:26][C:27](=[O:44])[C@@H:28]([NH2:36])[CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:9]1=[O:45])=[O:6])([CH3:4])([CH3:2])[CH3:3]

Participants

3

Reactant 1

HCID 206577841-tert-butylcarbonylmethyl-2-oxo-3-[(2S)-(2-tert-butoxycarbonylamino-3-phenylpropionyl)amino]-5-phenyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine

Product 1

HCID 20657781(-)-1-tert-butylcarbonylmethyl-2-oxo-3-[(2S)-(2-amino-3-phenylpropionyl)amino]-5-phenyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepineYield 47%

Reagents, catalysts & solvents 1

HCID 204431481,4-Dioxane hydrochlorideSolvent

Procedure

1-tert-Butylcarbonylmethyl-2-oxo-3-[(2S)-(2-tert-butoxycarbonylamino-3-phenylpropionyl)amino]-5-phenyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine (8.06 g) was dissolved in 4N HCl-dioxane (40 ml), the solution was stirred for one hour at room temperature. The reaction mixture was concentrated under reduced pressure, neutralized with saturated aqueous sodium bicarbonate, and extracted with methylene chloride. The organic layer was dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography(ethyl acetate contained water), to thereby obtain 3.01 g of (+)-1-tert-butylcarbonylmethyl-2-oxo-3-[(2S)-(2-amino-3-phenylpropionyl)amino]-5-phenyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine of first eluent and 3.17 g of (−)-1-tert-butylcarbonylmethyl-2-oxo-3-[(2S)-(2-amino-3-phenylpropionyl)amino]-5-phenyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine of second eluent.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. extractionextracted with methylene chloride
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography(ethyl acetate contained water)

Sources & evidence

ORD record
ord-4090caab35eb470388654644e99e3ec2
Source dataset
uspto-grants-2001_05
Patent number
US06239131B1

Reaction notes

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