4-Methylmorpholine → N-(N-benzyloxycarbonyl-2-amino-4-Pentenoyl)-L-valine benzyl ester

HRID 1067057Notes

Reaction equation

HRID 1067057 reaction equation
[CH2:1]([O:8][C:9]([NH:11][CH:12]([CH2:23][CH:24]=[CH2:25])[C:13]([NH:15][C@H:16]([C:20]([OH:22])=[O:21])[CH:17]([CH3:19])[CH3:18])=[O:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:26](OC(NC(CC=C)C(O)=O)=O)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.CN1CCOCC1.C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1>C(Cl)Cl>[CH2:26]([O:21][C:20](=[O:22])[C@H:16]([CH:17]([CH3:18])[CH3:19])[NH:15][C:13](=[O:14])[CH:12]([NH:11][C:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:10])[CH2:23][CH:24]=[CH2:25])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 134306152-(((Benzyloxy)carbonyl)amino)pent-4-enoic acidHCID 20662989N-(N-Benzyloxycarbonyl-2-Amino-4-Pentenoyl)-L-Valine

Product 1

HCID 20662988N-(N-benzyloxycarbonyl-2-amino-4-Pentenoyl)-L-valine benzyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N-(N-Benzyloxycarbonyl-2-Amino-4-Pentenoyl)-L-Valine Benzxyl Ester (4) To a cooled (0-5° C.) solution of 24 mg (0.096 mmol) N-(N-benzyloxycarbonyl-2-amino-4-pentenoic acid (3), 36 mg (0.096 mmol) valine benzyl ester p-toluenesulfonyl salt, and 11 μL (0.096 mmol) N-methylmorpholine in 2 mL CH2Cl2 was added 14 mg (0.101 mmol) HOBt and 21 mg (0.101 mmol) DCC and the mixture was stirred for 19 h. The solution was filtered and the filtrate diluted with 10 mL CH2Cl2 and washed with two 10-mL portions of 0.5 N HCl, with two 10-mL portions of saturated aqueous NaHCO3, and with 10 mL brine. The organic phase was dried (MgSO4) and concentrated. The crude product was applied to a silica gel column (1×15 cm) and elution with 5% MeOH in CH2Cl2 gave pure N-(N-benzyloxycarbonyl-2-amino-4-Pentenoyl)-L-valine benzyl ester (4) as a colorless oil: yield 35 mg (83%); 1H NMR (CDCl3) δ0.80-0.90 (m, 6H); 2.14-2.20 (m, 1H); 2.49-2.56 (m, 2H); 4.20-4.32 (M, 1H); 4.55-4.60 (m, 1H0; 5.07-5.30 (M, 6H); 5.65-5.83 (m, 1H); 6.42-6.49 (m, 1H); 7.30-7.34 (m, 10H); mass spectrum (CI, methane) m/z 439 (M+H)+, 225.

Workup

  1. filtrationThe solution was filtered
  2. additionthe filtrate diluted with 10 mL CH2Cl2
  3. washwashed with two 10-mL portions of 0.5 N HCl, with two 10-mL portions of saturated aqueous NaHCO3
  4. dry with materialThe organic phase was dried (MgSO4)
  5. concentrationconcentrated
  6. washThe crude product was applied to a silica gel column (1×15 cm) and elution with 5% MeOH in CH2Cl2

Sources & evidence

ORD record
ord-dc18691765764bbba5591eeada072b46
Source dataset
uspto-grants-2001_06
Patent number
US06245938B1

Reaction notes

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