1,2-Dichloroethane → N-Acetyl-tyrosinyl-valinyl-(4-phenoxy)proline Methyl Ester

HRID 502303Notes

Reaction equation

HRID 502303 reaction equation
[C:1]([NH:4][C@H:5]([C:14]([NH:16][C@H:17]([C:21]([OH:23])=O)[CH:18]([CH3:20])[CH3:19])=[O:15])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=1)(=[O:3])[CH3:2].[CH3:24][O:25][C:26](=[O:39])[C@@H:27]1[CH2:31][CH:30]([O:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH2:29][NH:28]1.C(N(C(C)C)CC)(C)C.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C)C=O.C(OCC)(=O)C.ClCCl>[CH3:24][O:25][C:26](=[O:39])[C@@H:27]1[CH2:31][CH:30]([O:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH2:29][N:28]1[C:21](=[O:23])[C@H:17]([CH:18]([CH3:19])[CH3:20])[NH:16][C:14](=[O:15])[C@H:5]([CH2:6][C:7]1[CH:8]=[CH:9][C:10]([OH:13])=[CH:11][CH:12]=1)[NH:4][C:1](=[O:3])[CH3:2]

Participants

9

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 22875497N-Acetyl-tyrosinyl-valineHCID 545742204-Phenoxyproline methyl ester

Product 1

HCID 54377655N-Acetyl-tyrosinyl-valinyl-(4-phenoxy)proline Methyl EsterYield 46.3%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

N-Acetyl-tyrosinyl-valine (0.524 g, 1.63 mmol) and 4-phenoxyproline methyl ester (0.381 g, 1.48 mmol) were dissolved in 4 ml each of dimethylformamide and dichloromethane and cooled to 0° C. To the cooled solution was added diisopropylethylamine (258 ul, 1.86 mmol), HOBT (0.24 g, 1.78 mmol), and EDC (0.37 g, 1.92 mmol) and the reaction was stirred for 18 hrs. The mixture was diluted with 400 ml of ethyl acetate and washed with water, 10% sodium hydrogen sulfate, 10% sodium bicarbonate, and water. The organic layer was concentrated to give a residue that was purified by flash chromatography (SiO2) eluting with 94:6:1 (CH2Cl2:i-PrOH:Pyridine) to afford 360 mg of the title compound.

Workup

  1. washwashed with water, 10% sodium hydrogen sulfate, 10% sodium bicarbonate, and water
  2. concentrationThe organic layer was concentrated
  3. customto give a residue that
  4. customwas purified by flash chromatography (SiO2)
  5. washeluting with 94:6:1 (CH2Cl2:i-PrOH:Pyridine)

Sources & evidence

ORD record
ord-432b00c601954d2aa54ab715a4086c32
Source dataset
uspto-grants-2010_08
Patent number
US07772366B2

Reaction notes

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