Ethylmorpholine → Z-Tyr(But)-Gly-OEt

HRID 1154150Notes

Reaction equation

HRID 1154150 reaction equation
C(N1CCOCC1)C.C1CCC(N=C=NC2CCCCC2)CC1.[NH:24]([C:41]([O:43][CH2:44][C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)=[O:42])[C@H:25]([C:38](O)=[O:39])[CH2:26][C:27]1[CH:32]=[CH:31][C:30]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[CH:29][CH:28]=1.[NH2:51][CH2:52][C:53]([O:55][CH2:56][CH3:57])=[O:54].Cl.C1C=CC2N(O)N=NC=2C=1>CN(C)C=O>[NH:24]([C:41]([O:43][CH2:44][C:45]1[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=1)=[O:42])[C@H:25]([C:38]([NH:51][CH2:52][C:53]([O:55][CH2:56][CH3:57])=[O:54])=[O:39])[CH2:26][C:27]1[CH:28]=[CH:29][C:30]([O:33][C:34]([CH3:35])([CH3:37])[CH3:36])=[CH:31][CH:32]=1

Participants

7

Reactant 5

HCID 7525EthylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 978520O-(1,1-Dimethylethyl)-N-((phenylmethoxy)carbonyl)-L-tyrosineHCID 2723640Glycine ethyl ester, hydrochloride

Product 1

HCID 13178769Z-Tyr(But)-Gly-OEt

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

6.4 ml (50 mmoles) of N-ethylmorpholine and 11.33 g (55 mmoles) of DCC are added at 0° C. and while stirring to a solution of 18.55 g (50 mmoles) of Z-Tyr(But)-OH, 6.98 g (50 mmoles) of H-Gly-OEt.HCl and 6.75 g (50 mmoles) of HOBt in 75 ml of dimethylformamide. The mixture is stirred for 2 hours at 0° C. and is allowed to stand overnight at room temperature. The precipitate is filtered off and the filtrate is concentrated in a high vacuum. The residue is partitioned between ethyl acetate and water. The ethyl acetate phase is extracted by shaking with NaHCO3 solution, a KHSO4 /K2SO4 buffer and water, and is dried over Na2SO4 and concentrated. The residue is dissolved in diisopropyl ether. Undissolved material is filtered off and petroleum ether is added to the filtrate. The mixture is cooled for a few hours in an ice bath and the precipitate is filtered off. Yield 20.63 g (89%), melting point 108° C. [α]D22 =-13.4° (c=1, methanol).

Workup

  1. waitto stand overnight at room temperature
  2. filtrationThe precipitate is filtered off
  3. concentrationthe filtrate is concentrated in a high vacuum
  4. customThe residue is partitioned between ethyl acetate and water
  5. extractionThe ethyl acetate phase is extracted
  6. stirringby shaking with NaHCO3 solution
  7. dry with materiala KHSO4 /K2SO4 buffer and water, and is dried over Na2SO4
  8. concentrationconcentrated
  9. dissolutionThe residue is dissolved in diisopropyl ether
  10. filtrationUndissolved material is filtered off
  11. additionpetroleum ether is added to the filtrate
  12. temperatureThe mixture is cooled for a few hours in an ice bath
  13. filtrationthe precipitate is filtered off
  14. customYield 20.63 g (89%), melting point 108° C. [α]D22 =-13.4° (c=1, methanol)

Sources & evidence

ORD record
ord-d695d153319a43da9eba32413d7b1a09
Source dataset
uspto-grants-1984_12
Patent number
US04487764

Reaction notes

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