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

HRID 280767Notes

Reaction equation

HRID 280767 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.C(OCC)(=O)C>[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

7

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 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

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 leaving a residue. 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 thus obtained solution was distilled under reduced pressure leaving a residue. 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. customleaving a residue
  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 thus obtained solution was distilled under reduced pressure
  8. customleaving a residue
  9. customThe residue was crystallized with a mixture of ethyl acetate and n-hexan

Sources & evidence

ORD record
ord-c0328950fdd947dab9f76405b6b7d35a
Source dataset
uspto-grants-1986_05
Patent number
US04590178

Reaction notes

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