Water → Z-Glu(Nle-OBzl)-OBzl

HRID 44153Notes

Reaction equation

HRID 44153 reaction equation
[NH2:1][C@H:2]([C:7]([O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:8])[CH2:3][CH2:4][CH2:5][CH3:6].Cl.[NH:18]([C:35]([O:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)=[O:36])[C@H:19]([C:25]([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26])[CH2:20][CH2:21][C:22](=O)[OH:23].C(N(CC)CC)C.C1C=CC2N(O)N=NC=2C=1.O.CCN=C=NCCCN(C)C.Cl>C(Cl)Cl>[NH:18]([C:35]([O:37][CH2:38][C:39]1[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=1)=[O:36])[C@H:19]([C:25]([O:27][CH2:28][C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1)=[O:26])[CH2:20][CH2:21][C:22]([NH:1][C@H:2]([C:7]([O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:8])[CH2:3][CH2:4][CH2:5][CH3:6])=[O:23]

Participants

8

Reactant 6

HCID 962WaterHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 6994031(4S)-5-(Benzyloxy)-4-(((benzyloxy)carbonyl)amino)-5-oxopentanoic acidHCID 70044109HCID 70044109, compound

Product 1

HCID 131730877Z-Glu(Nle-OBzl)-OBzl

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

The resulting H-Nle-OBzl.HCl was dissolved in methylene chloride (30 mL) and the resulting reaction solution was maintained at 0° C. To the reaction solution, Z-Glu-OBzl (N-α-carbobenzoxy-L-glutamic acid α-benzyl ester, 0.70 g, 1.90 mM), triethylamine (0.29 mL, 1.1 eq., 2.10 mM), HOBt.H2O (1-hydroxybenzotriazole hydrate, 0.32 g, 1.1 eq., 2.10 mM), and WSC.HCl (0.41 g, 1.1 eq., 2.10 mM) was added. The temperature of the reaction solution was gradually raised and stirred at room temperature overnight (16 hours). Then, the reaction mixture was concentrated under reduced pressure, ethyl acetate (100 mL) was added to the resulting residue, and the organic phase was then washed once with water (30 mL), twice with a 5% aqueous solution of citric acid (30 mL), once with a saturated common salt solution (30 mL), twice with a 5% aqueous solution of sodium hydrogen carbonate (30 mL) and once with a saturated common salt solution (30 mL). Then, the organic phase was dried over anhydrous magnesium sulfate. The magnesium sulfate was removed through filtration and the filtrate was concentrated under reduced pressure. The resulting residue was recrystallized from ethyl acetate and n-hexane, the crystals thus obtained were collected through filtration and dried under reduced pressure to give crystals of Z-Glu(Nle-OBzl)-OBzl (0.91 g).

Workup

  1. customthe resulting reaction solution
  2. temperatureThe temperature of the reaction solution was gradually raised
  3. concentrationThen, the reaction mixture was concentrated under reduced pressure, ethyl acetate (100 mL)
  4. additionwas added to the resulting residue
  5. washthe organic phase was then washed once with water (30 mL), twice with a 5% aqueous solution of citric acid (30 mL), once with a saturated common salt solution (30 mL), twice with a 5% aqueous solution of sodium hydrogen carbonate (30 mL) and once with a saturated common salt solution (30 mL)
  6. dry with materialThen, the organic phase was dried over anhydrous magnesium sulfate
  7. customThe magnesium sulfate was removed through filtration
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. customThe resulting residue was recrystallized from ethyl acetate and n-hexane
  10. customthe crystals thus obtained
  11. filtrationwere collected through filtration
  12. customdried under reduced pressure

Sources & evidence

ORD record
ord-3b0528561a354f1c88ccbcfb0f1e704c
Source dataset
uspto-grants-2013_09
Patent number
US08541379B2

Reaction notes

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