Potassium Iodide → 4-Benzyloxycarbonyl-1-(tert-butoxycarbonylamino)-2-oxo-1,2,3,4-tetrahydropyrazine

HRID 2086221Notes

Reaction equation

HRID 2086221 reaction equation
[C:1]([O:5][C:6]([NH:8][NH2:9])=[O:7])([CH3:4])([CH3:3])[CH3:2].CO[CH:12]([O:15]C)[CH2:13]Br.[C:17](=O)([O-])[O-].[K+].[K+].[I-].[K+].[OH2:25].[C:26]1([CH3:36])[CH:31]=[CH:30][C:29](S(O)(=O)=O)=[CH:28][CH:27]=1.[CH3:37][N:38]([CH:40]=[O:41])C>C1(C)C=CC=CC=1>[CH2:36]([O:25][C:40]([N:38]1[CH:37]=[CH:17][N:9]([NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[C:12](=[O:15])[CH2:13]1)=[O:41])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

8

Reactant 6

HCID 4875Potassium IodideHCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 70091tert-Butyl carbazateHCID 816722-Bromo-1,1-dimethoxyethaneHCID 521998p-Toluenesulfonic acid monohydrate

Product 1

HCID 227271614-Benzyloxycarbonyl-1-(tert-butoxycarbonylamino)-2-oxo-1,2,3,4-tetrahydropyrazine

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of tert-butoxycarbonylhydrazine (53 g), bromoacetoaldehyde dimethyl acetal (63.88 g), potassium carbonate (52 g) and potassium iodide (62.7 g) in DMF (350 ml) was stirred at 70° C. for 15 hours. Any insolubles were filtered off and the filtrate was combined with N-benzyloxycarbonyl glycine (79 g), HOBt (58 g) and WSC (87 g), and then stirred at room temperature for 15 hours. The reaction mixture was concentrated to obtain a residue, which was then partitioned between ethyl acetate and water, and the organic phase was washed with water, aqueous sodium bicarbonate, aqueous solution of citric acid and brine, dried and concentrated. The residue thus obtained was dissolved in toluene (1200 ml) and treated with p-toluenesulfonic acid hydrate (16.4 g) in 4 portions at an interval of 30 minutes, and stirred at 100° C. for 10 hours. The reaction mixture was washed with saturated aqueous sodium bicarbonate and brine, dried and concentrated. The residue thus obtained was purified by a column chromatography on a silica gel (hexane:ethyl acetate=3:1) to obtain 4-benzyloxycarbonyl-1-(tert-butoxycarbonylamino)-2-oxo-1,2,3,4-tetrahydropyrazine (19.36 g) as a colorless oil.

Workup

  1. filtrationAny insolubles were filtered off
  2. stirringstirred at room temperature for 15 hours
  3. concentrationThe reaction mixture was concentrated
  4. customto obtain a residue, which
  5. customwas then partitioned between ethyl acetate and water
  6. washthe organic phase was washed with water, aqueous sodium bicarbonate, aqueous solution of citric acid and brine
  7. customdried
  8. concentrationconcentrated
  9. customThe residue thus obtained
  10. stirringstirred at 100° C. for 10 hours
  11. washThe reaction mixture was washed with saturated aqueous sodium bicarbonate and brine
  12. customdried
  13. concentrationconcentrated
  14. customThe residue thus obtained
  15. customwas purified by a column chromatography on a silica gel (hexane:ethyl acetate=3:1)

Sources & evidence

ORD record
ord-c991f943aad745b992fa178eb574f1e0
Source dataset
uspto-grants-2004_04
Patent number
US06723722B1

Reaction notes

Loading…