Triethylamine → Z-Glu(Val-Gly-OBzl)-OBzl

HRID 424603Notes

Reaction equation

HRID 424603 reaction equation
[NH:1]([C:20]([O:22]C(C)(C)C)=O)[C@H:2]([C:6]([NH:8][CH2:9][C:10]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:11])=[O:7])[CH:3]([CH3:5])[CH3:4].Cl.O1CCOCC1.N[C@H](C(NCC(OCC1C=CC=CC=1)=O)=O)C(C)C.Cl.[NH:54]([C:71]([O:73][CH2:74][C:75]1[CH:80]=[CH:79][CH:78]=[CH:77][CH:76]=1)=[O:72])[C@H:55]([C:61]([O:63][CH2:64][C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=1)=[O:62])[CH2:56][CH2:57]C(=O)O.C(N(CC)CC)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>C(Cl)Cl>[NH:54]([C:71]([O:73][CH2:74][C:75]1[CH:76]=[CH:77][CH:78]=[CH:79][CH:80]=1)=[O:72])[C@H:55]([C:61]([O:63][CH2:64][C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=1)=[O:62])[CH2:56][CH2:57][C:20]([NH:1][C@H:2]([C:6]([NH:8][CH2:9][C:10]([O:12][CH2:13][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)=[O:11])=[O:7])[CH:3]([CH3:4])[CH3:5])=[O:22]

Participants

9

Reactant 7

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 6994031(4S)-5-(Benzyloxy)-4-(((benzyloxy)carbonyl)amino)-5-oxopentanoic acidHCID 13561799HCID 13561799, compoundHCID 204431481,4-Dioxane hydrochlorideHCID 131729421H-Val-Gly-OBzl.HCl

Product 1

HCID 131729420Z-Glu(Val-Gly-OBzl)-OBzlYield 70%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Boc-Val-Gly-OBzl (5.47 g, 15.0 mmol) was added to 4 N HCl/dioxane solution (40 ml), and the mixture was stirred at room temperature for 50 minutes. Dioxane was removed by concentration under reduced pressure, n-hexane (30 ml) was added to the residue, and the mixture was concentrated under reduced pressure. This procedure was repeated 3 times to quantitatively obtain H-Val-Gly-OBzl.HCl. Then, H-Val-Gly-OBzl.HCl and Z-Glu-OBzl (5.57 g, 15.0 mmol) were dissolved in methylene chloride (50 ml), and the solution was kept at 0° C. Triethylamine (2.30 ml, 16.5 mmol), HOBt (1-hydroxybenzotriazole, 2.53 g, 16.5 mmol), and WSC.HCl (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride, 3.16 g, 16.5 mmol) were added to the solution, and the mixture was stirred at room temperature for 2 days. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in heated ethyl acetate (1500 ml). The solution was washed with water (200 ml), 5% citric acid aqueous solution (200 ml×twice), saturated brine (150 ml), 5% sodium hydrogencarbonate aqueous solution (200 ml×twice), and saturated brine (150 ml). The organic layer was dried over anhydrous magnesium sulfate, then the magnesium sulfate was removed by filtration, and the filtrate was concentrated under reduced pressure. The deposited crystals were collected by filtration, and dried under reduced pressure to obtain white crystals of Z-Glu(Val-Gly-OBzl)-OBzl (6.51 g, 10.5 mmol).

Workup

  1. customDioxane was removed by concentration under reduced pressure, n-hexane (30 ml)
  2. additionwas added to the residue
  3. concentrationthe mixture was concentrated under reduced pressure
  4. customwas kept at 0° C
  5. stirringthe mixture was stirred at room temperature for 2 days
  6. concentrationThe reaction mixture was concentrated under reduced pressure
  7. dissolutionthe residue was dissolved in heated ethyl acetate (1500 ml)
  8. washThe solution was washed with water (200 ml), 5% citric acid aqueous solution (200 ml×twice), saturated brine (150 ml), 5% sodium hydrogencarbonate aqueous solution (200 ml×twice), and saturated brine (150 ml)
  9. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  10. customthe magnesium sulfate was removed by filtration
  11. concentrationthe filtrate was concentrated under reduced pressure
  12. filtrationThe deposited crystals were collected by filtration
  13. customdried under reduced pressure

Sources & evidence

ORD record
ord-833c422c9a1a49bfb01c4873cafcfadd
Source dataset
uspto-grants-2012_01
Patent number
US08106020B2

Reaction notes

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