HCID 151180, compound → HCID 131722374, compound

HRID 634626Notes

Reaction equation

HRID 634626 reaction equation
[NH:1]([C:18]([O:20]CC1C=CC=CC=1)=O)[C@H:2]([C:10]([NH:12][C@@H:13]([C:15]([OH:17])=[O:16])[CH3:14])=[O:11])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[H][H].[NH:30]([C:60]([O:62][C:63]([CH3:66])([CH3:65])[CH3:64])=[O:61])[C@@H:31](C(OC1C(F)=C(F)C(F)=C(F)C=1F)=O)[CH2:32][CH2:33][CH2:34][NH:35][C:36]([O:38][CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)=[O:37].N[C@H](C(N[C@@H](C(O)=O)C)=O)CC1C=CC=CC=1>CO.C(O)=O.[Pd].O1CCOCC1.O>[NH:30]([C:60]([O:62][C:63]([CH3:66])([CH3:65])[CH3:64])=[O:61])[C@@H:31]([C:18]([NH:1][C@H:2]([C:10]([NH:12][C@@H:13]([C:15]([OH:17])=[O:16])[CH3:14])=[O:11])[CH2:3][C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1)=[O:20])[CH2:32][CH2:33][CH2:34][NH:35][C:36]([O:38][CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)=[O:37]

Participants

10

Reactant 4

HCID 151180HCID 151180, compoundHCID 3008147D-Alanine, N-[(phenylmethoxy)carbonyl]-L-phenylalanyl-HCID 14392679HCID 14392679, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 131722374HCID 131722374, compound

Reagents, catalysts & solvents 5

HCID 23938PalladiumCatalystHCID 284Formic AcidSolventHCID 887MethanolSolventHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

6.5 g (18.0 mmol) of Z-Phe-D-Ala-OH was dissolved in 15 ml methanol and 2 ml formic acid. 0.2 g palladium catalyst was added and hydrogen was passed through the solution for 3 hours. The catalyst was removed by filtration, and the solvents were evaporated under vacuum. The residue was flooded with ether. The precipitate was filtered off, rinsed with ether and dried. The yield of H-Phe-D-Ala-OH was 5.3 g (98.1%). Rf=0.01 in chloroform:ethyl acetate:methanol:acetic acid=6:3:1:0.1. Rf=0.45 in acetic acid:chloroform:methanol=1:3:2:2. 8.0 g (15.0 mmol) of pentafluorophenyl ester of Boc-D-Orn(Z)-OPfp was dissolved in 15 ml dioxane. To this was added with mixing 4.3 g (17.7 mmol) H-Phe-D-Ala-OH dissolved in water with pH 8.5. The reaction mixture was stirred for a day and a night at room temperature. The solvents were evaporated under vacuum, 70 ml ethyl acetate was added, and the mixture was acidified to pH 2-3 by the addition of 2% sulfuric acid solution. The peptide was extracted twice with 70 ml ethyl acetate, washed with saturated sodium chloride solution to neutral pH and dried over anhydrous sodium sulfate. The solvent was removed by evaporation under vacuum leaving a thick oil. The product was crystallized from ethyl acetate with ether and hexane. The yield was 6.92 g (74.4%), and the melting point was 145° C. Rf=0.44 in acetic acid:chloroform;methanol=0.5:16:1. Rf=0.32 in chloroform:ethyl acetate:methanol=6:3:1.

Workup

  1. customThe catalyst was removed by filtration
  2. customthe solvents were evaporated under vacuum
  3. filtrationThe precipitate was filtered off
  4. washrinsed with ether
  5. customdried
  6. additionTo this was added
  7. customThe solvents were evaporated under vacuum, 70 ml ethyl acetate
  8. additionwas added
  9. additionthe mixture was acidified to pH 2-3 by the addition of 2% sulfuric acid solution
  10. extractionThe peptide was extracted twice with 70 ml ethyl acetate
  11. washwashed with saturated sodium chloride solution to neutral pH
  12. dry with materialdried over anhydrous sodium sulfate
  13. customThe solvent was removed by evaporation under vacuum
  14. customleaving a thick oil
  15. customThe product was crystallized from ethyl acetate with ether and hexane

Sources & evidence

ORD record
ord-6a235c9db3c04720991ff23d47d8940e
Source dataset
uspto-grants-2001_02
Patent number
US06184208B2

Reaction notes

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