Ethylmorpholine → L-glutamylphenylalanine benzyl ester

HRID 2309035Notes

Reaction equation

HRID 2309035 reaction equation
[NH2:1][C@H:2]([C:8]([OH:10])=O)[CH2:3][CH2:4][C:5]([OH:7])=[O:6].C1(C)C(S(O)(=O)=O)=CC=CC=1.[CH2:22]([O:29][C:30](=[O:40])[C@H:31]([CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[NH2:32])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C(N1CCOCC1)C.C1(N=C=NC2CCCCC2)CCCCC1>CN(C)C=O.ClCCl>[CH2:22]([O:29][C:30](=[O:40])[C@H:31]([CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[NH:32][C:8](=[O:10])[C@H:2]([CH2:3][CH2:4][C:5](=[O:6])[OH:7])[NH2:1])[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1

Participants

7

Reactant 4

HCID 7525EthylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 33032L-Glutamic AcidHCID 86587548L-phenylalanine benzyl ester toluenesulfonic acid

Product 1

HCID 86741776L-glutamylphenylalanine benzyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

A solution of 0.52 g of pyro-L-glutamic acid, 1.72 g of phenylalanine benzyl ester toluene sulfonic acid and 0.55 mg of N-ethylmorpholine in 5 ml of dimethylformamide (DMF) and 20 ml of dichloromethane was cooled in an ice bath with stirring. A solution of 0.826 g of dicyclohexylcarbodiimide in 2 ml dichloromethane was added to the above reaction mixture. The reaction mixture was stirred in an ice water bath for 1 hour and then at room temperature overnight. Dicyclohexylurea was removed by filtration and the product was washed in ethyl acetate. Solvents of the combined filtrates were removed under reduced pressure with a rotary evaporator at 40°. Ethyl acetate (25 ml) was added to the residue and the organic solution was washed unit neutral. The organic phase was dried over anhydrous MgSO4, filtered and then the solvent was removed with a rotary evaporator. The material was crystallized from isopropanol and ether, yield; 1.01 g of white needles, m.p. 103°-104.5° C. The material was shown to be homogeneous by paper electrophoresis and by TLC with five separate solvent systems. Elemental analysis yielded the following results:

Workup

  1. stirringThe reaction mixture was stirred in an ice water bath for 1 hour
  2. customat room temperature
  3. customovernight
  4. customDicyclohexylurea was removed by filtration
  5. washthe product was washed in ethyl acetate
  6. customSolvents of the combined filtrates were removed under reduced pressure with a rotary evaporator at 40°
  7. additionEthyl acetate (25 ml) was added to the residue
  8. washthe organic solution was washed unit neutral
  9. dry with materialThe organic phase was dried over anhydrous MgSO4
  10. filtrationfiltered
  11. customthe solvent was removed with a rotary evaporator
  12. customThe material was crystallized from isopropanol and ether, yield; 1.01 g of white needles, m.p. 103°-104.5° C
  13. customseparate solvent systems
  14. customElemental analysis yielded the
  15. customfollowing results

Sources & evidence

ORD record
ord-e55d13cb48b44989a5cd9e7ba8c95b52
Source dataset
uspto-grants-1987_09
Patent number
US04692458

Reaction notes

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