Glycolic Acid → 1,3-Diethyl 2-[(2-hydroxyacetyl)amino]propanedioate

HRID 1639166Notes

Reaction equation

HRID 1639166 reaction equation
Cl.[NH2:2][CH:3]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[C:4]([O:6][CH2:7][CH3:8])=[O:5].[C:14](O)(=[O:17])[CH2:15][OH:16].ON1C2C=CC=CC=2N=N1.C1(N=C=NC2CCCCC2)CCCCC1>CN(C)C=O.C(N(CC)CC)C>[OH:17][CH2:14][C:15]([NH:2][CH:3]([C:4]([O:6][CH2:7][CH3:8])=[O:5])[C:9]([O:11][CH2:12][CH3:13])=[O:10])=[O:16]

Participants

7

Reactant 4

HCID 757Glycolic AcidHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 3084143Propanedioic acid, 2-amino-, 1,3-diethyl ester, hydrochloride (1:1)

Product 1

HCID 150963891,3-Diethyl 2-[(2-hydroxyacetyl)amino]propanedioateYield 62.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of diethyl 2-aminomalonate hydrochloride (4.2 g) and glycolic acid (1.6 g) in dimethylformamide is added triethylamine (2.12 g), and to the mixture are added 1-hydroxybenzotriazole (2.7 g) and N,N'-dicyclohexylcarbodiimide (4.33 g) with stirring under ice cooling. The mixture is reacted at 0° to 5° C. for 2 hours and further reacted at room temperature for 15 hours. The reaction mixture is concentrated under reduced pressure, and to the residue is added ethyl acetate, and the undissolved substance is filtered off. The filtrate is washed with aqueous sodium carbonate solution, dried and then the solvent is distilled off. The residue is purified by silica gel column chromatography [solvent: chloroform-ethyl acetate (2:1)] to give diethyl 2-[(hydroxyacetyl)amino]malonate (2.9 g), m.p. 74°-74.5° C.

Workup

  1. customThe mixture is reacted at 0° to 5° C. for 2 hours
  2. customfurther reacted at room temperature for 15 hours
  3. concentrationThe reaction mixture is concentrated under reduced pressure
  4. additionto the residue is added ethyl acetate
  5. filtrationthe undissolved substance is filtered off
  6. washThe filtrate is washed with aqueous sodium carbonate solution
  7. customdried
  8. distillationthe solvent is distilled off
  9. customThe residue is purified by silica gel column chromatography [solvent: chloroform-ethyl acetate (2:1)]

Sources & evidence

ORD record
ord-e3aa62b4d44a4aa38f564b34d11c3aed
Source dataset
uspto-grants-1989_11
Patent number
US04882447

Reaction notes

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