Dicyclohexylcarbodiimide → Nalpha-Benzyloxycarbonyl-D-alanyl-L-leucine methyl ester

HRID 437329Notes

Reaction equation

HRID 437329 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@@H:12]([C:14]([OH:16])=O)[CH3:13])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH3:18][O:19][C:20](=[O:27])[C@H:21]([CH2:23][CH:24]([CH3:26])[CH3:25])[NH2:22].ON1C2C=CC=CC=2N=N1.C1(N=C=NC2CCCCC2)CCCCC1>C(N(CC)CC)C.CN(C)C=O>[CH3:18][O:19][C:20](=[O:27])[C@H:21]([CH2:23][CH:24]([CH3:26])[CH3:25])[NH:22][C:14](=[O:16])[C@@H:12]([CH3:13])[NH:11][C:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:10]

Participants

7

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 70832N-Cbz-d-alanineHCID 757711-HydroxybenzotriazoleHCID 2723695Leucine methyl ester hydrochloride

Product 1

HCID 14278860Nalpha-Benzyloxycarbonyl-D-alanyl-L-leucine methyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
-10 °C

Procedure

Nα-Benzyloxycarbonyl-D-alanine, 8.92 g., 40 mmol, L-leucine methyl ester hydrochloride, 7.28 g., 40 mmol and 1-hydroxybenztriazole, 5.4 g., 40 mmol are dissolved in 100 ml. of dimethylformamide and the solution stirred and cooled to -10° C. Triethylamine, 5.6 ml., 40 mmol, is added and after fifteen minutes the solution is treated with 8.6 g., 42 mmol, of dicyclohexylcarbodiimide and stirred for 2 to 3 hours in a cooling bath and then to room temperature overnight. The mixture is filtered and the filtrate evaporated. The residue is dissolved in ethyl acetate and washed with 5% sodium bicarbonate solution, dilute hydrochloric acid and saturated sodium chloride solution, dried over magnesium sulfate and evaporated. The residue is crystallized twice from etherpetroleum ether, 12.88 g.; m.p. 65°-68° C.

Workup

  1. dissolution, 40 mmol are dissolved in 100 ml
  2. addition, 40 mmol, is added and after fifteen minutes the solution
  3. additionis treated with 8.6 g
  4. customto room temperature
  5. customovernight
  6. filtrationThe mixture is filtered
  7. customthe filtrate evaporated
  8. dissolutionThe residue is dissolved in ethyl acetate
  9. washwashed with 5% sodium bicarbonate solution, dilute hydrochloric acid and saturated sodium chloride solution
  10. dry with materialdried over magnesium sulfate
  11. customevaporated
  12. customThe residue is crystallized twice from etherpetroleum ether, 12.88 g

Sources & evidence

ORD record
ord-4c8d7897a2754ffca10acad66a83f697
Source dataset
uspto-grants-1977_06
Patent number
US04031071

Reaction notes

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