Citric Acid → Cbz-Phe-NH-C2H4-NH-Boc

HRID 416543Notes

Reaction equation

HRID 416543 reaction equation
[C:1]([NH:11][C@H:12]([C:20]([OH:22])=O)[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].Cl.[C:24]([O:28][C:29]([NH:31][CH2:32][CH2:33][NH2:34])=[O:30])([CH3:27])([CH3:26])[CH3:25].O.ON1C2C=CC=CC=2N=N1.CN1CCOCC1.Cl.C(N=C=NCCCN(C)C)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C)C=O.C(Cl)(Cl)Cl.CO>[NH:11]([C:1]([O:3][CH2:4][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1)=[O:2])[C@H:12]([C:20]([NH:34][CH2:33][CH2:32][NH:31][C:29]([O:28][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:30])=[O:22])[CH2:13][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

10

Reactant 6

HCID 311Citric AcidHCID 79724-MethylmorpholineHCID 70878Benzyloxycarbonyl-L-phenylalanineHCID 187200tert-Butyl N-(2-aminoethyl)carbamate hydrochlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrate

Product 1

HCID 20769586Cbz-Phe-NH-C2H4-NH-BocYield 86.4%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent

Procedure

N-carbobenzoxy-L-phenylalanine (Cbz-Phe: 7.16 g, 25.4 mmol), N-t-butoxycarbonyl-ethylenediamine hydrochloride (5.00 g, 25.4 mmol), 1-hydroxybenzotriazole hydrate (HOBT: 4.28 g, 28.0 mmol), and N-methylmorpholine (NMM: 3.07 mL, 28.0 mmol) were dissolved in 100 mL of dimethylformamide (DMF), to which 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC: 5.36 g, 28.0 mmol) was then added under stirring and cooling with ice, followed by stirring at room temperature for one day. A 10% citric acid aqueous solution was added to the reaction solution, and the precipitated solid was dissolved in chloroform and a small amount of methanol, followed by washing the solution with a saturated sodium bicarbonate solution and a saturated saline solution before drying with sodium sulfate. It was concentrated under reduced pressure, followed by purifying the resultant residue using silica gel column chromatography (elution solvent: chloroform:methanol=95:5) to provide 9.69 g of the title compound as a white solid.

Workup

  1. additionwas then added
  2. temperaturecooling with ice
  3. stirringby stirring at room temperature for one day
  4. washby washing the solution with a saturated sodium bicarbonate solution
  5. dry with materiala saturated saline solution before drying with sodium sulfate
  6. concentrationIt was concentrated under reduced pressure
  7. customby purifying the resultant residue
  8. washsilica gel column chromatography (elution solvent: chloroform:methanol=95:5)

Sources & evidence

ORD record
ord-869c691ddf4d448192af73fed021eb41
Source dataset
uspto-grants-2012_01
Patent number
US08088916B2

Reaction notes

Loading…