Citric Acid → HCID 131721198, compound

HRID 1954682Notes

Reaction equation

HRID 1954682 reaction equation
[N:1]1([C:16]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[O:17])[CH2:15][CH2:14][CH2:13][CH2:12][C@@H:2]1[C:3]([NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:4].Br[CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29].[H-].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCCC1>[N:1]1([C:16]([O:18][CH2:19][C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)=[O:17])[CH2:15][CH2:14][CH2:13][CH2:12][C@@H:2]1[C:3]([N:5]([C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1)[CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29])=[O:4]

Participants

6

Reactant 4

HCID 311Citric AcidHCID 7748Ethyl bromoacetateHCID 24758Sodium hydrideHCID 131721199HCID 131721199, compound

Product 1

HCID 131721198HCID 131721198, compoundYield 96%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of Cbz-D-hPro-NHC6H5 (7.7 g, 22.8 mmol) in tetrahydrofuran (300 mL) was added ethyl bromoacetate (12.6 mL, 113.8 mmol). The solution was cooled to 0° C. and NaH 60% suspension (2 g, 50 mmol) was added in small portions over 20 minutes, with gas evolution. After gas evolution had ceased, the cold bath was left unattended and the mixture was allowed to warm slowly to room temperature. After 18 hours, 1N citric acid (50 mL) was added slowly with cooling. The mixture was partitioned between ethyl acetate (300 mL) and 1N citric acid (300 mL) The organic layer was washed twice with 1N citric acid (200 mL), twice with saturated aqueous NaHCO3, and twice with saturated aqueous sodium chloride solution. The ethyl acetate layer was dried (MgSO4), filtered and concentrated in vacuo. The residue was chromatographed over silica gel, eluting with a step gradient of hexanes through 50% ethyl acetate/hexanes. Fractions containing product (as judged by TLC) were combined and concentrated in vacuo to give a yellow oil (9.2 g, 96%).

Workup

  1. waitthe cold bath was left
  2. temperatureto warm slowly to room temperature
  3. temperaturewith cooling
  4. customThe mixture was partitioned between ethyl acetate (300 mL) and 1N citric acid (300 mL) The organic layer
  5. washwas washed twice with 1N citric acid (200 mL), twice with saturated aqueous NaHCO3
  6. dry with materialThe ethyl acetate layer was dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was chromatographed over silica gel
  10. washeluting with a step gradient of hexanes through 50% ethyl acetate/hexanes
  11. additionFractions containing product (as judged by TLC)
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8ed2a1e4d6a149d6bf10dd6a687d61c0
Source dataset
uspto-grants-2000_09
Patent number
US06124277

Reaction notes

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