Triethylamine → D-Alanyl-alpha-L-aspartyl-D-alanine isopropyl ester

HRID 868650Notes

Reaction equation

HRID 868650 reaction equation
[CH2:1]([N:3](CC)CC)[CH3:2].Cl.[CH:9]([O:12][C:13](=[O:17])[C@@H:14]([CH3:16])[NH2:15])([CH3:11])[CH3:10].[NH:18]([C:34]([O:36]CC1C=CC=CC=1)=O)[C@H:19]([C:31]([OH:33])=O)[CH2:20][C:21](=[O:30])[O:22]CC1C=CC=CC=1.C1CCC(N=C=NC2CCCCC2)CC1>C(Cl)(Cl)Cl>[CH:9]([O:12][C:13](=[O:17])[C@@H:14]([CH3:16])[NH:15][C:31](=[O:33])[C@H:19]([CH2:20][C:21](=[O:30])[OH:22])[NH:18][C:34](=[O:36])[C@@H:1]([CH3:2])[NH2:3])([CH3:11])[CH3:10]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 10868DicyclohexylcarbodiimideHCID 476024-(Phenylmethyl) hydrogen N-((phenylmethoxy)carbonyl)-L-aspartateHCID 51064150propan-2-yl (2R)-2-aminopropanoate hydrochloride

Product 1

HCID 14151478D-Alanyl-alpha-L-aspartyl-D-alanine isopropyl ester

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Procedure

Triethylamine (1.4 ml) was added to a suspension of D-alanine isopropyl ester hydrochloride (1.7 g) in 50 ml of chloroform. To the resulting solution was admixed Z-Asp(OBzl) (3.6 g), a solution of 2.06 g DCC in 10 ml chloroform was added under ice cooling, and the mixture was stirred under ice cooling for one hour and then at room temperature overnight. Precipitated dicyclohexylurea was filtered off, the filtrate was concentrated under reduced pressure, and the residue was dissolved in 150 ml of ethyl acetate. This solution was washed with 2N-HCl, water, 4% aqueous solution of sodium bicarbonate, water and saturated aqueous solution of sodium chloride in that order, and dried over anhydrous sodium sulfate. After filtering off the drying agent, the filtrate was concentrated under reduced pressure. The residue was dissolved in 100 ml of 80% acetic acid, and the solution was subjected to catalytic reduction under a hydrogen gas stream at room temperature for four hours using palladium-carbon as catalyst. After filtering off the catalyst, the filtrate was concentrated under reduced pressure, and the residue was recrystallized from water, giving 1.8 g of D-alanyl-α-L-aspartyl-D-alanine isopropyl ester.

Workup

  1. customat room temperature
  2. customovernight
  3. filtrationPrecipitated dicyclohexylurea was filtered off
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. dissolutionthe residue was dissolved in 150 ml of ethyl acetate
  6. washThis solution was washed with 2N-HCl, water, 4% aqueous solution of sodium bicarbonate, water and saturated aqueous solution of sodium chloride in that order
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationAfter filtering off the drying agent
  9. concentrationthe filtrate was concentrated under reduced pressure
  10. dissolutionThe residue was dissolved in 100 ml of 80% acetic acid
  11. customat room temperature
  12. customfor four hours
  13. filtrationAfter filtering off the catalyst
  14. concentrationthe filtrate was concentrated under reduced pressure
  15. customthe residue was recrystallized from water

Sources & evidence

ORD record
ord-1cc1060d678c4dfba45fb7cc8d5a3898
Source dataset
uspto-grants-1988_10
Patent number
US04780528

Reaction notes

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