1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 4-Benzyloxycarbonyl-1-(tert-butoxycarbonylamino)-2-oxo-1,2,3,4-tetrahydropyrazine

HRID 2086220Notes

Reaction equation

HRID 2086220 reaction equation
[C:1]([O:5][C:6]([NH:8][NH2:9])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:10]([O:17][C:18]([N:20]([CH2:25][CH:26](OCC)OCC)[CH2:21][C:22](O)=[O:23])=[O:19])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.CCN=C=NCCCN(C)C.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C(#N)C.C1(C)C=CC=CC=1>[CH2:10]([O:17][C:18]([N:20]1[CH:25]=[CH:26][N:9]([NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[C:22](=[O:23])[CH2:21]1)=[O:19])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 70091tert-Butyl carbazateHCID 521998p-Toluenesulfonic acid monohydrateHCID 53725139N-benzyloxycarbonyl-N-(2,2-diethoxyethyl) glycine

Product 1

HCID 227271614-Benzyloxycarbonyl-1-(tert-butoxycarbonylamino)-2-oxo-1,2,3,4-tetrahydropyrazineYield 17.7%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6342AcetonitrileSolvent

Procedure

A solution of tert-butoxycarbonylhydrazine (3.96 g) and N-benzyloxycarbonyl-N-(2,2-diethoxyethyl) glycine (9.76 g) in acetonitrile (100 ml) was treated with WSC (5.75 g) and stirred at room temperature for 15 hours. The reaction mixture was concentrated to obtain a residue, which was partitioned between ethyl acetate and water, and then the organic phase was washed with water, aqueous sodium bicarbonate, aqueous solution of citric acid and brine, dried and then concentrated. The residue obtained was dissolved in toluene (200 ml), combined with p-toluenesulfonic acid hydrate (285 mg) and then stirred at 100° C. for 90 minutes. The reaction mixture was washed with saturated aqueous sodium bicarbonate and brine, dried and then concentrated. The residue thus obtained was purified by a column chromatography on a silica gel (hexane:ethyl acetate=3:2) to obtain 4-benzyloxycarbonyl-1-(tert-butoxycarbonylamino)-2-oxo-1,2,3,4-tetrahydropyrazine (1.84 g) as a colorless oil.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customto obtain a residue, which
  3. customwas partitioned between ethyl acetate and water
  4. washthe organic phase was washed with water, aqueous sodium bicarbonate, aqueous solution of citric acid and brine
  5. customdried
  6. concentrationconcentrated
  7. customThe residue obtained
  8. stirringstirred at 100° C. for 90 minutes
  9. washThe reaction mixture was washed with saturated aqueous sodium bicarbonate and brine
  10. customdried
  11. concentrationconcentrated
  12. customThe residue thus obtained
  13. customwas purified by a column chromatography on a silica gel (hexane:ethyl acetate=3:2)

Sources & evidence

ORD record
ord-e4c235c1ecba427291adc775be33bf54
Source dataset
uspto-grants-2004_04
Patent number
US06723722B1

Reaction notes

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