Chloroform → Ethyl N-(1-((benzyloxy)carbonyl)-L-prolyl)-L-leucinate

HRID 1733653Notes

Reaction equation

HRID 1733653 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:18][CH2:17][CH2:16][C@H:12]1[C:13]([OH:15])=O)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH2:20]([O:22][C:23](=[O:30])[C@H:24]([CH2:26][CH:27]([CH3:29])[CH3:28])[NH2:25])[CH3:21].C(Cl)(Cl)Cl.C1(C)C=CC(S(ON=C(C#N)C(OCC)=O)(=O)=O)=CC=1>C(N(CC)CC)C>[CH2:20]([O:22][C:23](=[O:30])[C@H:24]([CH2:26][CH:27]([CH3:29])[CH3:28])[NH:25][C:13](=[O:15])[C@@H:12]1[CH2:16][CH2:17][CH2:18][N:11]1[C:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:10])[CH3:21]

Participants

6

Reactant 4

HCID 6212ChloroformHCID 101987Benzyloxycarbonyl-L-prolineHCID 2786718Ethyl 2-(p-toluenesulfonyloxyimino)-2-cyanoacetateHCID 11658447L-Leucine, ethyl ester, hydrochloride (1:1)

Product 1

HCID 6453075Ethyl N-(1-((benzyloxy)carbonyl)-L-prolyl)-L-leucinateYield 4.1%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

N-Benzyloxycarbonyl-L-proline (1.25 g) and L-leucine ethyl ester hydrochloride (1.0 g) are suspended into chloroform (10 ml), and therein is dissolved triethylamine (1.4 ml). To the solution is added ethyl 2-(p-toluenesulfonyloxyimino)-2-cyanoacetate (1.5 g) and the mixture is stirred at room temperature for 16 hours. After reaction, the reaction mixture is extracted with ethyl acetate. The exatract is washed with water, 1 N aqueous sodium hydrogen carbonate, water, 1 N hydrochloric acid and water in order and then dried over anhydrous magnesium sulfate. After drying, the solvent is distilled off and the residual oily substance (1.6 g) is dissolved in chloroform and then the mixture is subjected to a silica gel column chromatography (developer: chloroform). The first fraction thus obtained is concentrated and the resulting residue is crystallized from ether-petroleum ether to give N-(N-benzyloxycarbonyl-L-prolyl)-L-leucine ethyl ester (80 mg), melting point: 60°-64° C. The product is identified with an authentic sample by infrared spectrum.

Workup

  1. customAfter reaction
  2. extractionthe reaction mixture is extracted with ethyl acetate
  3. washThe exatract is washed with water, 1 N aqueous sodium hydrogen carbonate, water, 1 N hydrochloric acid and water in order
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customAfter drying
  6. distillationthe solvent is distilled off
  7. dissolutionthe residual oily substance (1.6 g) is dissolved in chloroform
  8. customThe first fraction thus obtained
  9. concentrationis concentrated
  10. customthe resulting residue is crystallized from ether-petroleum ether

Sources & evidence

ORD record
ord-b51b60f2a1244096b8d3f14c0d875741
Source dataset
uspto-grants-1980_12
Patent number
US04242507

Reaction notes

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