Benzyloxycarbonylglycine → (S)-4-benzyloxycarbonylaminoacetyl-3-(3-t-butoxycarbonylaminopropyl)-2-oxopiperazine-1-acetic acid t-butyl ester

HRID 376534Notes

Reaction equation

HRID 376534 reaction equation
C(O)(=O)C(O)=O.[C:7]([O:11][C:12](=[O:32])[CH2:13][N:14]1[CH2:19][CH2:18][NH:17][C@@H:16]([CH2:20][CH2:21][CH2:22][NH:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C:15]1=[O:31])([CH3:10])([CH3:9])[CH3:8].[NH:33]([C:38]([O:40][CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)=[O:39])[CH2:34][C:35](O)=[O:36].Cl.C(N=C=NCCCN(C)C)C>C(=O)([O-])O.[Na+].CC(C)=O>[C:7]([O:11][C:12](=[O:32])[CH2:13][N:14]1[CH2:19][CH2:18][N:17]([C:35](=[O:36])[CH2:34][NH:33][C:38]([O:40][CH2:41][C:42]2[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=2)=[O:39])[C@@H:16]([CH2:20][CH2:21][CH2:22][NH:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C:15]1=[O:31])([CH3:9])([CH3:8])[CH3:10]

Participants

6

Reactant 3

HCID 14349BenzyloxycarbonylglycineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 70045951(s)-3-(3-t-Butoxycarbonylaminopropyl)-2-oxopiperazine-1-acetic acid t-butyl ester oxalate

Product 1

HCID 10907851(S)-4-benzyloxycarbonylaminoacetyl-3-(3-t-butoxycarbonylaminopropyl)-2-oxopiperazine-1-acetic acid t-butyl esterYield 100%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

In a saturated aqueous solution of sodium hydrogencarbonate was dissolved (S)-3-(3-t-butoxycarbonylaminopropyl)-2-oxopiperazine-1-acetic acid t-butyl ester oxalate (1.6 g, 3.47 mmol). The solution was subjected to extraction with ethyl acetate, and the extract solution was concentrated under reduced pressure. The concentrate and N-Z-Gly-OH (0.87 g, 4.16 mmol) were dissolved in 16.0 cc of acetone. To the solution was added, at 15° C. under stirring, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.87 g, 4.51 mmol). The mixture was stirred for one hour at room temperature, and the reaction mixture was concentrated under reduced pressure. The concentrate was washed with a 5% aqueous solution of potassium hydrogensulfate and a saturated aqueous solution of sodium hydrogencarbonate. The organic layer was concentrated under reduced pressure, and the concentrate was purified by means of a silica gel column chromatography (ethyl acetate) to afford 1.95 g (100%) of the titled compound as a colorless amorphous powdery product.

Workup

  1. extractionThe solution was subjected to extraction with ethyl acetate
  2. concentrationthe extract solution was concentrated under reduced pressure
  3. concentrationThe concentrate
  4. additionTo the solution was added, at 15° C.
  5. stirringThe mixture was stirred for one hour at room temperature
  6. concentrationthe reaction mixture was concentrated under reduced pressure
  7. washThe concentrate was washed with a 5% aqueous solution of potassium hydrogensulfate
  8. concentrationThe organic layer was concentrated under reduced pressure
  9. customthe concentrate was purified by means of a silica gel column chromatography (ethyl acetate)

Sources & evidence

ORD record
ord-56d650a50670416db711588cd859f4e8
Source dataset
uspto-grants-2000_02
Patent number
US06020334

Reaction notes

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