Benzyloxycarbonyl-L-phenylalanine → Methyl(s)-2-[(s)-2-((s)-2-benzyloxycarbonylamino-3-phenyl-propionylamino)-3-methylbutyrylamino]-3-methylbutyrate

HRID 1943302Notes

Reaction equation

HRID 1943302 reaction equation
[NH:1]([C:13]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:14])[C@H:2]([C:10]([OH:12])=O)[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.CCN(C(C)C)C(C)C.[NH2:54][C@@H:55]([CH:67]([CH3:69])[CH3:68])[C:56]([NH:58][C@@H:59]([CH:64]([CH3:66])[CH3:65])[C:60]([O:62][CH3:63])=[O:61])=[O:57].C([O-])(O)=O.[Na+]>CN(C=O)C>[CH2:16]([O:15][C:13]([NH:1][C@@H:2]([CH2:3][C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1)[C:10]([NH:54][C@@H:55]([CH:67]([CH3:69])[CH3:68])[C:56]([NH:58][C@@H:59]([CH:64]([CH3:65])[CH3:66])[C:60]([O:62][CH3:63])=[O:61])=[O:57])=[O:12])=[O:14])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

8

Reactant 6

HCID 70878Benzyloxycarbonyl-L-phenylalanineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 12944632L-valyl L-valine methyl ester

Product 1

HCID 23278816Methyl(s)-2-[(s)-2-((s)-2-benzyloxycarbonylamino-3-phenyl-propionylamino)-3-methylbutyrylamino]-3-methylbutyrateYield 74.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

247 mg of Z-Phe-OH (0.825 mmol, 1 eq) were dissolved in 10 ml of dry DMF at 0° C. under argon. Then 56 mg of 1-hydroxybenzotriazole (0.5 eq), 221 mg of 1-ethyl-3-(dimethylaminopropyl)carbodiimide hydrochloride (1.4 eq) and 346 μl of Hünig's base (2.4 eq) were added, and the mixture was stirred for 30 min. 190 mg of the compound from Example 143a) were then added, and the mixture was stirred at RT for 20 h. The reaction mixture was mixed with 50 ml of saturated NaHCO3 solution and extracted with ethyl acetatet (2×30 ml). The organic phase was dried over Na2SO4, filtered and concentrated. The crude product was chromatographed on silica gel with heptane/ethyl acetate mixtures. 314 mg of the desired compound were obtained.

Workup

  1. stirringthe mixture was stirred at RT for 20 h
  2. extractionextracted with ethyl acetatet (2×30 ml)
  3. dry with materialThe organic phase was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was chromatographed on silica gel with heptane/ethyl acetate mixtures

Sources & evidence

ORD record
ord-5c8b0776d7bc440a880d8baa04131f6e
Source dataset
uspto-grants-2013_03
Patent number
US08389764B2

Reaction notes

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