Z-Phe-ONp → Z-Phe-Val-N-Me-Tyr(3-tBu)-NH2

HRID 1383722Notes

Reaction equation

HRID 1383722 reaction equation
[NH:1](C(OC(C)(C)C)=O)[C@H:2]([C:6]([N:8]([CH3:25])[C@H:9]([C:22]([NH2:24])=[O:23])[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[C:13]([C:18]([CH3:21])([CH3:20])[CH3:19])[CH:12]=1)=[O:7])[CH:3]([CH3:5])[CH3:4].N[C@H](C(N(C)[C@H](C(N)=O)CC1C=CC(O)=C(C(C)(C)C)C=1)=O)C(C)C.[CH:58]1[CH:63]=[CH:62][C:61]([CH2:64][C@H:65]([NH:78][C:79]([O:81][CH2:82][C:83]2[CH:88]=[CH:87][CH:86]=[CH:85][CH:84]=2)=[O:80])[C:66](OC2C=CC([N+]([O-])=O)=CC=2)=[O:67])=[CH:60][CH:59]=1>C(Cl)Cl.C(O)(C(F)(F)F)=O.CN(C=O)C.CN(C1C=CN=CC=1)C.C(OCC)(=O)C>[NH:78]([C:79]([O:81][CH2:82][C:83]1[CH:88]=[CH:87][CH:86]=[CH:85][CH:84]=1)=[O:80])[C@H:65]([C:66]([NH:1][C@H:2]([C:6]([N:8]([CH3:25])[C@H:9]([C:22]([NH2:24])=[O:23])[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[C:13]([C:18]([CH3:21])([CH3:19])[CH3:20])[CH:12]=1)=[O:7])[CH:3]([CH3:5])[CH3:4])=[O:67])[CH2:64][C:61]1[CH:60]=[CH:59][CH:58]=[CH:63][CH:62]=1

Participants

9

Reactant 3

HCID 151025Z-Phe-ONpHCID 131722737Boc-Val-N-Me-Tyr(3-tBu)-NH2HCID 131722740Val-N-Me-Tyr(3-tBu)-NH2

Product 1

HCID 131722739Z-Phe-Val-N-Me-Tyr(3-tBu)-NH2

Reagents, catalysts & solvents 5

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 146 mg (0.325 mmol) of Boc-Val-N-Me-Tyr(3-tBu)-NH2 in 2 ml of methylene chloride, 1 ml of TFA was added and the mixture was stirred at room temperature for 30 minutes. The solvent was distilled off under reduced pressure. To a solution of the resulting TFA salt of Val-N-Me-Tyr(3-tBu)-NH2 in 2 ml of DMF, 0.1 ml of TEA, 219 mg (0.348 mmol) of Z-Phe-ONp and 93.5 mg (0.765 mmol) of DMAP were added and the mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with ethyl acetate and washed first with saturated aqueous NaHCO3, then with water and finally with saturated brine. The organic layer was dried with anhydrous magnesium sulfate and concentrated under reduced pressure; the resulting residue was subjected to silica gel column chromatography (eluting solvent; ethyl acetate:n-hexane=1:1) to give Z-Phe-Val-N-Me-Tyr(3-tBu)-NH2 in the amount of 189 mg (92%).

Workup

  1. distillationThe solvent was distilled off under reduced pressure
  2. stirringthe mixture was stirred at room temperature for 2 hours
  3. washwashed first with saturated aqueous NaHCO3
  4. dry with materialThe organic layer was dried with anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. washthe resulting residue was subjected to silica gel column chromatography (eluting solvent; ethyl acetate:n-hexane=1:1)

Sources & evidence

ORD record
ord-c8c41c1ee69e4625a1b4a44dacda4158
Source dataset
uspto-grants-2001_07
Patent number
US06255285B1

Reaction notes

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