Dimethylformamide → Tyr-Ile

HRID 1283373Notes

Reaction equation

HRID 1283373 reaction equation
ClC1C=C(Cl)C(Cl)=CC=1O[C:11](=[O:32])[C@H:12]([CH2:24][C:25]1[CH:30]=[CH:29][C:28]([OH:31])=[CH:27][CH:26]=1)[NH:13]C(OCC1C=CC=CC=1)=O.[NH2:33][C@H:34]([C:39]([OH:41])=[O:40])[C@H:35]([CH2:37][CH3:38])[CH3:36].CN(C)C=O.CN1CCOCC1>O>[NH2:13][C@H:12]([C:11]([NH:33][C@H:34]([C:39]([OH:41])=[O:40])[C@H:35]([CH2:37][CH3:38])[CH3:36])=[O:32])[CH2:24][C:25]1[CH:26]=[CH:27][C:28]([OH:31])=[CH:29][CH:30]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 6306L-Isoleucine2×HCID 79724-MethylmorpholineHCID 53673208HCID 53673208, compound

Product 1

HCID 7019110Tyr-Ile

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Carbobenzoxytyrosine 2,4,5-trichlorophenyl ester (544 parts) is added to a suspension of 131 parts of isoleucine in 2000 parts by volume of dimethylformamide. After adding 101 parts of N-methylmorpholine, the mixture is stirred 48 hours at room temperature. Unreacted isoleucine is still present. Water (500 parts by volume) is added and stirring is continued for another 48 hours. The mixture is concentrated to dryness under high vacuum at 40°. The residue is dissolved in 2000 parts by volume of ethyl acetate, the ethyl acetate is washed with four 2000 parts by volume portions of 0.2 M potassium bisulfate, dried over sodium sulfate and stripped under reduced pressure. The residue is dissolved in 1 l. of chloroform and the solution added dropwise with violent stirring to 20 l. of ether. The resulting white powder, carbobenzoxy=tyrosylisoleucine, (42.8 parts) 0.1 mole, is dissolved in 500 parts by volume of 90% acetic acid and hydrogenated at 60 psi at room temperature over 4.3 parts of palladium black. Hydrogen uptake stopped after 2 hours. The catalyst is filtered off and the filtrate concentrated to dryness under vacuum. The residue is rubbed with ether yielding tyrosylisoleucine, Tyr-Ile.

Workup

  1. stirringstirring
  2. waitis continued for another 48 hours
  3. concentrationThe mixture is concentrated to dryness under high vacuum at 40°
  4. dissolutionThe residue is dissolved in 2000 parts by volume of ethyl acetate
  5. washthe ethyl acetate is washed with four 2000 parts by volume portions of 0.2 M potassium bisulfate
  6. dry with materialdried over sodium sulfate
  7. dissolutionThe residue is dissolved in 1 l
  8. additionof chloroform and the solution added dropwise
  9. stirringwith violent stirring to 20 l
  10. dissolutionThe resulting white powder, carbobenzoxy=tyrosylisoleucine, (42.8 parts) 0.1 mole, is dissolved in 500 parts by volume of 90% acetic acid and hydrogenated at 60 psi at room temperature over 4.3 parts of palladium black
  11. waitHydrogen uptake stopped after 2 hours
  12. filtrationThe catalyst is filtered off
  13. concentrationthe filtrate concentrated to dryness under vacuum

Sources & evidence

ORD record
ord-cd37f054b5264356bf8ebfaeaf3e5dd5
Source dataset
uspto-grants-1976_08
Patent number
US03975365

Reaction notes

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