1-Hydroxybenzotriazole → Boc-Leu-DTrp-OBzl

HRID 977516

Reaktionsgleichung

Reaktionsgleichung von HRID 977516
[NH:1]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C@H:2]([C:7]([OH:9])=O)[CH2:3][CH:4]([CH3:6])[CH3:5].O.[NH2:18][C@@H:19]([C:30]([O:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)=[O:31])[CH2:20][C:21]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[NH:23][CH:22]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>ClCCl.O>[NH:1]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C@H:2]([C:7]([NH:18][C@@H:19]([C:30]([O:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)=[O:31])[CH2:20][C:21]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[NH:23][CH:22]=1)=[O:9])[CH2:3][CH:4]([CH3:5])[CH3:6]

Komponenten

7

Edukt 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 6995075D-Tryptophan benzyl esterHCID 12373896N-Boc-L-Leucine Hydrate

Produkt 1

HCID 131719296Boc-Leu-DTrp-OBzlAusbeute 95,8 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a mixture of Boc-Leu-OH.H2O (2.5 g), H-DTrp-OBzl (2.9 g) and HOBT.H2O (1.6 g) in dichloromethane (50 ml) was added EDCI.HCl (2.0 g) under ice cooling. After being stirred at room temperature for 16 h, the mixture was washed with water, 10% aq. citric acid, sat. aq. NaHCO3 and brine successively, dried over MgSO4 and evaporated in vacuo. The residue was triturated with hexane to give Boc-Leu-DTrp-OBzl (4.79 g). To a solution of the dipeptide (753 mg) in dichloromethane (7 ml) were added methyl chloroformate (1 ml), pulverized NaOH (89 mg) and TBAHS (20 mg) under ice cooling. After being stirred of the mixture at room temperature for 30 min, pulverized NaOH (89 mg) was added. This procedure was repeated twice more. The reaction mixture was diluted with dichloromethane, washed with sat. aq. NaHCO3, 10% aq. citric acid, water and brine successively, dried over MgSO4 and evaporated in vacuo. The residue was recrystallized from dichloromethane and petroleum ether to give Boc-Leu-DTrp(COOMe)-OBzl (721 mg) as colorless crystals. The dipeptide (708 mg) was dissolved in methanol (7 ml)--THF (5 ml) and 10% Pd/C (70 mg) was added. The mixture was vigorously stirred at room temperature under an atmospheric pressure of hydrogen for 1 h. The reaction mixture was filtered and the filtrate was evaporated in vacuo to give Boc-Leu-DTrp(COOMe)-OH (580 mg).

Aufarbeitung

  1. washthe mixture was washed with water, 10% aq. citric acid, sat. aq. NaHCO3 and brine successively
  2. dry with materialdried over MgSO4
  3. customevaporated in vacuo
  4. customThe residue was triturated with hexane

Quellen und Nachweise

ORD-Eintrag
ord-526ebbf475b945109e6e1cce8d26498c
Quelldatensatz
uspto-grants-1997_03
Patentnummer
US05614498

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