Dicyclohexylamine → Benzyl 2-[[2-[[2-[(2-methylpropan-2-yl)oxycarbonylamino]acetyl]amino]acetyl]amino]acetate

HRID 378196Notes

Reaction equation

HRID 378196 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1(NC2CCCCC2)CCCCC1.Cl.[CH2:27]([O:34][C:35](=[O:42])[CH2:36][NH:37][C:38](=[O:41])[CH2:39][NH2:40])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.CCN=C=NCCCN(C)C>C(Cl)(Cl)Cl.C(Cl)Cl.C(OCC)(=O)C.C(Cl)(Cl)Cl>[CH2:27]([O:34][C:35](=[O:42])[CH2:36][NH:37][C:38](=[O:41])[CH2:39][NH:40][C:10](=[O:12])[CH2:9][NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1

Participants

7

Reactant 4

HCID 7582DicyclohexylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 78288N-(tert-butoxycarbonyl)glycineHCID 13996146Glycyl-glycine benzyl ester hydrochloride

Product 1

HCID 434010Benzyl 2-[[2-[[2-[(2-methylpropan-2-yl)oxycarbonylamino]acetyl]amino]acetyl]amino]acetateYield 86%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 19352771Chloroform methylene chloride ethyl acetateSolvent

Procedure

In 380 ml of a chloroform/methylene chloride/ethyl acetate (7:5:1 by volume) mixed solvent were dissolved 7.13 g (20 mmol) of t-butyloxycarbonylglycine. dicyclohexylamine and 5.18 g (20 mmol) of glycylglycine benzyl ester hydrochloride obtained in Example 1. To this solution, 50 ml of a chloroform solution containing 4.22 g (20 mmol) of EDAC were added at -5° C. with stirring. The resulting mixture was stirred for 24 hours. The resulting chloroform solution was successively washed twice with a 10% by weight aqueous citric acid solution, then twice with water, then twice with a 4% by weight aqueous sodium hydrogen carbonate solution and finally twice with water. Thereafter, the organic phase was dried over anhydrous sodium sulfate. The solvent was then completely removed in vacuo to obtain a white oily material. This was crystallized from hexane to obtain 6.52 g (yield: 86%) of t-butyloxycarbonyl-glycylglycylglycine benzyl ester as a white solid. This benzyl ester was dispersed, to which 130 ml of 4N HCl/ethyl acetate were added. The mixture was stirred for 4 hours and then the solvent was removed in vacuo to obtain white precipitates. The precipitates were washed well with diethyl ether to obtain 4.63 g (yield: 85%) of glycylglycylglycine benzyl ester hydrochloride as a white solid having the following physical properties:

Workup

  1. additionwere added at -5° C.
  2. stirringThe resulting mixture was stirred for 24 hours
  3. washThe resulting chloroform solution was successively washed twice with a 10% by weight aqueous citric acid solution
  4. dry with materialThereafter, the organic phase was dried over anhydrous sodium sulfate
  5. customThe solvent was then completely removed in vacuo
  6. customto obtain a white oily material
  7. customThis was crystallized from hexane

Sources & evidence

ORD record
ord-956801869e6841b49e2619ea0884fe48
Source dataset
uspto-grants-2000_02
Patent number
US06030640

Reaction notes

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