Isoamyl Nitrite → Boc-Leu-DTrp-betaAla-OEt

HRID 1757293Notes

Reaction equation

HRID 1757293 reaction equation
[NH:1]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[C@H:2]([C:7]([NH:9][C@@H:10]([C:21]([NH:23]N)=[O:22])[CH2:11][C:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[NH:14][CH:13]=1)=[O:8])[CH2:3][CH:4]([CH3:6])[CH3:5].N(OCCC(C)C)=O.N[CH2:41][CH2:42][C:43]([O:45][CH2:46][CH3:47])=[O:44].Cl>CN(C=O)C>[NH:1]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[C@H:2]([C:7]([NH:9][C@@H:10]([C:21]([NH:23][CH2:41][CH2:42][C:43]([O:45][CH2:46][CH3:47])=[O:44])=[O:22])[CH2:11][C:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[NH:14][CH:13]=1)=[O:8])[CH2:3][CH:4]([CH3:6])[CH3:5]

Participants

5

Reactant 3

HCID 8053Isoamyl NitriteHCID 458475beta-Alanine, ethyl ester, hydrochlorideHCID 11070055Boc-Leu-DTrp-NHNH2

Product 1

HCID 131719104Boc-Leu-DTrp-betaAla-OEtYield 87.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
-20 °C

Procedure

To a solution of Boc-Leu-DTrp-NHNH2 (39 mg) obtained in Example 1-(2) in DMF (0.5 ml ) was added 3.1 M HCl/14,-dioxane (81 μl) at -60° C. The temperature of the solution was raised to -20° C. and isoamyl nitrite (15 μl) was added. The reaction mixture was stirred at -20° C. to -15° C. for 1.5 h and cooled at -60° C. A solution of βAla-OEt.HCl (17 mg) in DMF (0.5 ml) and TEA (50 μl) were added. The reaction mixture was stirred at 5° C. overnight and concentrated under reduced pressure. The residue was partitioned between water and dichloromethane. The organic layer was washed with water, dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by preparative TLC (Merck, Kieselgel 60 F254) with chloroform/methanol=30/1 for development to give the product (41 mg).

Workup

  1. temperaturecooled at -60° C
  2. stirringThe reaction mixture was stirred at 5° C. overnight
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was partitioned between water and dichloromethane
  5. washThe organic layer was washed with water
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by preparative TLC (Merck, Kieselgel 60 F254) with chloroform/methanol=30/1 for development

Sources & evidence

ORD record
ord-8eef6de2576c4673b9b2caf80b9bf68f
Source dataset
uspto-grants-1995_08
Patent number
US05444152

Reaction notes

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