Hydrochloric Acid → 2,4-Bis-(4-hydroxybenzyl)-3-azaglutaric acid-diisopropyl ester

HRID 1418795

Reaction equation

HRID 1418795 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9](=O)[C:10]([OH:12])=[O:11])=[CH:4][CH:3]=1.[NH2:14][C@H:15]([C:24]([OH:26])=[O:25])[CH2:16][C:17]1[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=1.[BH4-].[Na+].Cl>CO>[CH:2]([O:25][C:24](=[O:26])[CH:15]([CH2:16][C:17]1[CH:18]=[CH:19][C:20]([OH:23])=[CH:21][CH:22]=1)[NH:14][CH:9]([CH2:8][C:5]1[CH:6]=[CH:7][C:2]([OH:1])=[CH:3][CH:4]=1)[C:10]([O:12][CH:5]([CH3:6])[CH3:4])=[O:11])([CH3:7])[CH3:3]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 9794-Hydroxyphenylpyruvic AcidHCID 6057L-TyrosineHCID 4311764Sodium borohydride

Product 1

HCID 541248932,4-Bis-(4-hydroxybenzyl)-3-azaglutaric acid-diisopropyl ester

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

9.01 g (50.0 mmol) of 4-hydroxyphenylpyruvic acid and 9.06 g (50.0 mmol) of tyrosine are dissolved in 60 ml of methanol and stirred for six hours at 60° C. Then, it is allowed to cool to room temperature and 0.76 g (20 mmol) of sodium borohydride is added. It is allowed to stir overnight and then the reaction mixture is mixed carefully with diluted hydrochloric acid until no more gas generation can be observed. The reaction mixture is concentrated by evaporation and dried in an oil pump vacuum for several hours at 100° C. The residue is taken up in isopropanol. Hydrogen chloride gas is introduced until saturation is achieved, stirred for two hours at room temperature and then for eight hours at 85° C. Then, it is concentrated by evaporation, the residue is dispersed between ethyl acetate and sodium bicarbonate solution, the organic phase is dried on sodium sulfate, filtered and concentrated by evaporation. The residue is chromatographed on silica gel with use of hexane/ethyl acetate as mobile solvent. The fractions that contain the pure product are combined and concentrated by evaporation.

Workup

  1. temperatureto cool to room temperature
  2. stirringto stir overnight
  3. concentrationThe reaction mixture is concentrated by evaporation
  4. customdried in an oil pump vacuum for several hours at 100° C
  5. additionHydrogen chloride gas is introduced until saturation
  6. stirringstirred for two hours at room temperature
  7. waitfor eight hours at 85° C
  8. concentrationThen, it is concentrated by evaporation
  9. additionthe residue is dispersed between ethyl acetate and sodium bicarbonate solution
  10. customthe organic phase is dried on sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated by evaporation
  13. customThe residue is chromatographed on silica gel with use of hexane/ethyl acetate as mobile solvent
  14. concentrationconcentrated by evaporation

Sources & evidence

ORD record
ord-c6b07bea86aa4d50a788a18adb7070a3
Source dataset
uspto-grants-1999_03
Patent number
US05885548

Linked notes

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