Dicyclohexylcarbodiimide → HCID 178523875, compound

HRID 1659808Notes

Reaction equation

HRID 1659808 reaction equation
Cl.Cl.C[O:4][C:5](=[O:14])[C@H:6]([CH2:8][C:9]1[N:13]=[CH:12][NH:11][CH:10]=1)[NH2:7].[CH:15]1([C:20](O)=[O:21])[CH2:19][CH2:18][CH2:17][CH2:16]1.C1CCC(N=C=NC2CCCCC2)CC1>O1CCOCC1.[OH-].[Na+]>[NH:11]1[CH2:10][CH2:9][CH2:8][C@H:6]1[C:5]([OH:4])=[O:14].[CH:15]1([C:20]([NH:7][C@H:6]([C:5]([OH:4])=[O:14])[CH2:8][C:9]2[N:13]=[CH:12][NH:11][CH:10]=2)=[O:21])[CH2:19][CH2:18][CH2:17][CH2:16]1

Participants

6

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 18840Cyclopentanecarboxylic acidHCID 178419105HCID 178419105, compound

Product 1

HCID 178523875HCID 178523875, compound

Reagents, catalysts & solvents 2

HCID 14798Sodium HydroxideSolventHCID 312751,4-DioxaneSolvent

Procedure

To the free base of Histidine methyl ester dihydrochloride, (m.p. 206°-207° C.), 2 mmoles of cyclopentane carboxylic acid and 2.2 mmoles of DCCI were added. The resulting dipeptide was purified by preparatory TLC with CHCl3 /MeOH (7/1) as the stationary phase. An oily residue was obtained, which was then dissolved in dioxane and hydrolyzed by NaOH. After acidification to neutralize and lyophilization, the residue was treated with dry purified methanol and filtered to remove insoluble sodium chloride. The product was coupled in dimethylformamide with proline using DCCI and 1-hydroxy-benzotriazole. The reaction mixture after 48 hours in an ice-salt bath (-10° C.) was immediately applied to a Sephadex G-≅column, and purified by gel filtration column chromatography. Fractions eluted from the column that showed a positive Pauley reaction (diazo sulfanillic acid reaction) were pooled together and lyophilized. A white fluffy product results. Yield-(30-40%).

Workup

  1. customThe resulting dipeptide was purified by preparatory TLC with CHCl3 /MeOH (7/1) as the stationary phase
  2. customAn oily residue was obtained
  3. additionlyophilization, the residue was treated
  4. customwith dry
  5. custompurified methanol
  6. filtrationfiltered
  7. customto remove insoluble sodium chloride
  8. filtrationpurified by gel filtration column chromatography
  9. washFractions eluted from the column that
  10. customa positive Pauley reaction (diazo sulfanillic acid reaction)
  11. customA white fluffy product results

Sources & evidence

ORD record
ord-109781b05f5e496296ae04bc9708d4d9
Source dataset
uspto-grants-1981_12
Patent number
US04305872

Reaction notes

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