Citric Acid → N-(2-{[(Benzyloxy)(hydroxy)methylidene]amino}-1-hydroxy-3-methylpentylidene)glycine

HRID 971549Notes

Reaction equation

HRID 971549 reaction equation
[NH:1]([C:10]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:11])[C@H:2]([C:7]([OH:9])=O)[C@H:3]([CH2:5][CH3:6])[CH3:4].CCCCC(F)(F)C(O)CC[C@@H]1[C@@H](CCCCC[CH2:39][C:40]([OH:42])=[O:41])C(=O)C[C@H]1O.C1CCC([NH:53]C2CCCCC2)CC1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(OCC)(=O)C>[NH:1]([C:10]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:11])[C@H:2]([C:7]([NH:53][CH2:39][C:40]([OH:42])=[O:41])=[O:9])[C@H:3]([CH2:5][CH3:6])[CH3:4]

Participants

4

Reactant 2

HCID 311Citric AcidHCID 131709977HCID 131709977, compound

Product 1

HCID 114630N-(2-{[(Benzyloxy)(hydroxy)methylidene]amino}-1-hydroxy-3-methylpentylidene)glycine

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

2.23 g of Z-Ile-OH-dicyclohexylammonium salt are suspended in ethyl acetate and acidified with 0.2 M citric acid. The resulting ethyl acetate solution is washed until neutral, dried and evaporated to dryness. The residue is dissolved in 15 ml of acetonitrile, and 750 mg of H-Gly-OMe.HCl are added to the solution followed at 0° C., with stirring, by 0.84 ml of triethylamine. After 10 minutes 1.24 g of dicyclohexylcarbodiimide are added and the mixture is stirred overnight at 0° C. The precipitate is filtered off, the filtrate evaporated to dryness, and the residue taken up in 30 ml of ethyl acetate and filtered. The ethyl acetate solution is washed with 0.2 M citric acid and saturated sodium bicarbonate solution, dried and concentrated to about 10 ml in vacuo. After adding 25 ml of hexane the protected dipeptide crystallises out; melting point 120°-122° C. Rf = 0.53 in the system chloroform-methanol (95:5) in a thin layer chromatogram on silica gel.

Workup

  1. washThe resulting ethyl acetate solution is washed until neutral,
  2. customdried
  3. customevaporated to dryness
  4. dissolutionThe residue is dissolved in 15 ml of acetonitrile
  5. addition750 mg of H-Gly-OMe.HCl are added to the solution
  6. customfollowed at 0° C.
  7. additionAfter 10 minutes 1.24 g of dicyclohexylcarbodiimide are added
  8. stirringthe mixture is stirred overnight at 0° C
  9. filtrationThe precipitate is filtered off
  10. customthe filtrate evaporated to dryness
  11. filtrationfiltered
  12. washThe ethyl acetate solution is washed with 0.2 M citric acid and saturated sodium bicarbonate solution
  13. customdried
  14. concentrationconcentrated to about 10 ml in vacuo
  15. additionAfter adding 25 ml of hexane the protected dipeptide
  16. customcrystallises out

Sources & evidence

ORD record
ord-1a3622a1c59141ac85b5bff79ec75de1
Source dataset
uspto-grants-1979_07
Patent number
US04159981

Reaction notes

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