1,2-Dichloroethane → Cbz-PhePhe-NH-C2H4-NH-Boc

HRID 1157432Notes

Reaction equation

HRID 1157432 reaction equation
[NH:1]([C:23](OCC1C=CC=CC=1)=[O:24])[C@H:2]([C:10]([NH:12][CH2:13][CH2:14][NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[O:11])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[NH:33]([C:45]([O:47][CH2:48][C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)=[O:46])[C@H:34](C(O)=O)[CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.C(Cl)CCl>CO.CN(C)C=O.[C].[Pd].O>[NH:33]([C:45]([O:47][CH2:48][C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)=[O:46])[C@H:34]([C:23]([NH:1][C@H:2]([C:10]([NH:12][CH2:13][CH2:14][NH:15][C:16]([O:18][C:19]([CH3:20])([CH3:21])[CH3:22])=[O:17])=[O:11])[CH2:3][C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1)=[O:24])[CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1

Participants

10

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 70878Benzyloxycarbonyl-L-phenylalanineHCID 757711-HydroxybenzotriazoleHCID 20769586Cbz-Phe-NH-C2H4-NH-Boc

Product 1

HCID 131728357Cbz-PhePhe-NH-C2H4-NH-BocYield 99.3%

Reagents, catalysts & solvents 4

HCID 178418390HCID 178418390, compoundCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Compound 1a (9.69 g, 21.9 mmol) was dissolved in 200 mL of methanol, to which 500 mg of 10% palladium carbon was then added, followed by stirring at room temperature for one day under an atmosphere of hydrogen. The catalyst was filtered off from the reaction mixture, followed by concentration under reduced pressure. This residue, Cbz-Phe (6.92 g, 23.1 mmol), HOBT (3.71 g, 24.2 mmol), and NMM (2.66 mL, 24.2 mmol) were dissolved in 50 mL of dimethylformamide (DMF), to which EDC (4.64 g, 24.2 mmol) was then added under stirring and cooling with ice, followed by stirring at room temperature for one day. Water was added to the reaction solution, which was then washed with a 10% citric acid aqueous solution, a saturated sodium bicarbonate solution, and water before drying. The resultant residue was purified using silica gel column chromatography (elution solvent: chloroform:methanol=90:10) to provide 12.8 g of the title compound as a white solid.

Workup

  1. additionwas then added
  2. filtrationThe catalyst was filtered off from the reaction mixture
  3. concentrationfollowed by concentration under reduced pressure
  4. additionwas then added
  5. stirringunder stirring
  6. temperaturecooling with ice
  7. stirringby stirring at room temperature for one day
  8. washwas then washed with a 10% citric acid aqueous solution
  9. dry with materiala saturated sodium bicarbonate solution, and water before drying
  10. customThe resultant residue was purified
  11. washsilica gel column chromatography (elution solvent: chloroform:methanol=90:10)

Sources & evidence

ORD record
ord-743b7882b779442baf554e339768e190
Source dataset
uspto-grants-2010_10
Patent number
US07807675B2

Reaction notes

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