Benzyloxycarbonylglycine → Ethyl 4-{[(benzyloxy)carbonyl]amino}-3-oxobutanoate

HRID 2186489Notes

Reaction equation

HRID 2186489 reaction equation
[CH2:1]([O:8][C:9]([NH:11][CH2:12][C:13]([OH:15])=O)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.[CH2:28]([O:30][C:31](=[O:36])[CH2:32]C([O-])=O)[CH3:29].[K+].[Cl-].[Mg+2].[Cl-]>C(#N)C>[CH2:1]([O:8][C:9]([NH:11][CH2:12][C:13](=[O:15])[CH2:32][C:31]([O:30][CH2:28][CH3:29])=[O:36])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 14349BenzyloxycarbonylglycineHCID 682631,1'-CarbonyldiimidazoleHCID 3446434Potassium ethyl malonateHCID 5360315Magnesium Chloride

Product 1

HCID 10265597Ethyl 4-{[(benzyloxy)carbonyl]amino}-3-oxobutanoateYield 100.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
23 °C

Procedure

In a 1 liter four-necked flask were charged 50 g (0.24 mol) of N-benzyloxycarbonylglycine and 300 ml of acetonitrile in a nitrogen stream, and 39.5 g (0.24 mol) of 1,1′-carbonyldiimidazole was added thereto over 30 minutes, followed by stirring at room temperature (22 to 24° C.) for 2 hours. After cooling to 7° C., 61.0 g (0.36 mol) of potassium malonate ethyl ester was added over 5 minutes, and 23.0 g (0.24 mol) of magnesium chloride was added over 30 minutes, followed by stirring at room temperature for 30 minutes and then at 50° C. for 2 hours to complete the reaction. Acetonitrile was removed by evaporation under reduced pressure, and 550 ml of a 5% hydrochloric acid aqueous solution was added to the reaction. The mixture was extracted and washed with 180 ml of butyl acetate. The organic layer was further washed with 100 ml of a 5% hydrochloric acid aqueous solution, neutralized with 100 ml of a 8% sodium carbonate aqueous solution, and washed with 100 ml of water. The solvent was removed by evaporation under reduced pressure to yield 67.1 g (90% as purified by column chromatography) of ethyl 4-benzyloxycarbonylamino-3-oxobutyrate as liquid.

Workup

  1. additionwas added
  2. temperatureAfter cooling to 7° C.
  3. stirringby stirring at room temperature for 30 minutes
  4. waitat 50° C. for 2 hours to complete
  5. customthe reaction
  6. customAcetonitrile was removed by evaporation under reduced pressure, and 550 ml of a 5% hydrochloric acid aqueous solution
  7. additionwas added to the reaction
  8. extractionThe mixture was extracted
  9. washwashed with 180 ml of butyl acetate
  10. washThe organic layer was further washed with 100 ml of a 5% hydrochloric acid aqueous solution
  11. washwashed with 100 ml of water
  12. customThe solvent was removed by evaporation under reduced pressure

Sources & evidence

ORD record
ord-22f1506f8a524adbacc8df5e1c53b68f
Source dataset
uspto-grants-2002_06
Patent number
US06403804B1

Reaction notes

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