Dicyclohexylcarbodiimide → Boc-Gly-Lys(Z)-OBzl

HRID 892416Notes

Reaction equation

HRID 892416 reaction equation
[NH2:1][C@H:2]([C:18]([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19])[CH2:3][CH2:4][CH2:5][CH2:6][NH:7][C:8]([O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:9].Cl.[NH:29]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:30][C:31](O)=[O:32].C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1>CN(C)C=O.C(N(CC)CC)C>[NH:29]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:30][C:31]([NH:1][C@H:2]([C:18]([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19])[CH2:3][CH2:4][CH2:5][CH2:6][NH:7][C:8]([O:10][CH2:11][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)=[O:9])=[O:32]

Participants

7

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 78288N-(tert-butoxycarbonyl)glycineHCID 11750132L-Lysine, N6-((phenylmethoxy)carbonyl)-, phenylmethyl ester, hydrochloride (1:1)

Product 1

HCID 14154103Boc-Gly-Lys(Z)-OBzlYield 80%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8471TriethylamineSolvent

Conditions

Temperature
4 °C

Procedure

To a solution of 20.35 g of H-Lys(Z)-OBzl.HCl (manufactured by Kokusan Kagaku) in 35 ml of dimethylformamide (called DMF hereinbelow), after neutralized by addition under cooling with ice of 7 ml of triethylamine, were added 8.76 g of Boc-Gly-OH (manufactured by Kokusan Kagaku), 7.43 g of HOBt (manufactured by Kokusan Kagaku) and 11.35 g of DCC (manufactured by Kokusan Kagaku). The mixture was stirred for 3 hours and at 4° C. for additional 16 hours. Dicyclohexylurea by-product was removed by filtration followed by addition of 300 ml of ethyl acetate. The resulting mixture was washed successively with saturated aqueous sodium chloride, 8% by weight aqueous sodium carbonate, saturated aqueous sodium chloride, 8% by weight aqueous citric acid and saturated aqueous sodium chloride. From the ethyl acetate layer, after dried over anhydrous sodium sulfate, was removed the solvent, and the residue was again dissolved in a small amount of ethyl acetate. From the solution after filtered, the solvent was completely distilled off to give 21.1 g (80% yield) of Boc-Gly-Lys(Z)-OBzl as an oily substance.

Workup

  1. additionafter neutralized by addition
  2. customDicyclohexylurea by-product was removed by filtration
  3. additionfollowed by addition of 300 ml of ethyl acetate
  4. washThe resulting mixture was washed successively with saturated aqueous sodium chloride, 8% by weight aqueous sodium carbonate, saturated aqueous sodium chloride, 8% by weight aqueous citric acid and saturated aqueous sodium chloride
  5. dry with materialFrom the ethyl acetate layer, after dried over anhydrous sodium sulfate
  6. customwas removed the solvent
  7. dissolutionthe residue was again dissolved in a small amount of ethyl acetate
  8. filtrationFrom the solution after filtered
  9. distillationthe solvent was completely distilled off

Sources & evidence

ORD record
ord-b4bf60390765484a820e4dfa37a12dfa
Source dataset
uspto-grants-1992_06
Patent number
US05118669

Reaction notes

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