1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → N-t-butyloxycarbonyl-L-alanyl-L-prolyl-L-proline benzylester

HRID 485572Notes

Reaction equation

HRID 485572 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:11]([N:13]1[CH2:20][CH2:19][CH2:18][C@H:14]1[C:15]([OH:17])=O)=[O:12])[CH3:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[CH2:22]([O:29][C:30](=[O:36])[C@@H:31]1[CH2:35][CH2:34][CH2:33][NH:32]1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>C(Cl)Cl>[CH2:22]([O:29][C:30](=[O:36])[C@@H:31]1[CH2:35][CH2:34][CH2:33][N:32]1[C:15](=[O:17])[C@@H:14]1[CH2:18][CH2:19][CH2:20][N:13]1[C:11](=[O:12])[C@H:9]([CH3:10])[NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 2733413Proline benzyl ester hydrochlorideHCID 11902919Boc-ala-pro-OH

Product 1

HCID 13389836N-t-butyloxycarbonyl-L-alanyl-L-prolyl-L-proline benzylesterYield 88.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-15 °C

Procedure

N-t-butyloxycarbonyl-L-alanyl-L-proline (4.3 g, 15 m mole), L-proline benzyl ester hydrochloride (3.7 g, 15.3 m mole) and HOBt (2.0 g, 15 m mole) were dissolved in methylene dichloride (40 ml). WSC (2.8 ml) was added dropwise to the above mixture while cooling to -15° C. and stirring. The reaction was carried out for 3 hours at a temperature of not more than 0° C., and then overnight at room temperature. The solvent was removed by distillation under reduced pressure. The residue was dissolved in ethyl acetate, and washed with 1N hydrochloric acid, water, 5% sodium bicarbonate and water, in order. The mixture was dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The residue was crystallized with a mixture of ethyl acetate and n-hexan to give a crystal of N-t-butyloxycarbonyl-L-alanyl-L-prolyl-L-proline benzyl ester (6.3 g, 88.7%) having melting point of 143° to 145° C. and specific rotatory power of [α]D25 =-131.0° (C=1, chloroform).

Workup

  1. customovernight
  2. customat room temperature
  3. customThe solvent was removed by distillation under reduced pressure
  4. dissolutionThe residue was dissolved in ethyl acetate
  5. washwashed with 1N hydrochloric acid, water, 5% sodium bicarbonate and water, in order
  6. dry with materialThe mixture was dried over anhydrous sodium sulfate
  7. distillationThe solvent was distilled off under reduced pressure
  8. customThe residue was crystallized with a mixture of ethyl acetate and n-hexan

Sources & evidence

ORD record
ord-7f5c582b04404c12a8cbda1ba3587ad8
Source dataset
uspto-grants-1985_08
Patent number
US04536395

Reaction notes

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