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

HRID 442005Notes

Reaction equation

HRID 442005 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.C(N(CC)CC)C.C1(N=C=NC2CCCCC2)CCCCC1>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 5

HCID 8471TriethylamineHCID 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 1

HCID 6228DimethylformamideSolvent

Procedure

Nα -Benzyloxycarbonyl-D-alanyl-L-leucine methyl ester is prepared from 8.92 g. (40 mmol) of Nα -benzyloxycarbonyl-D-alanine, 7.28 g. (40 mmol) of L-leucine methyl ester hydrochloride and 5.4 g. (40 mmol) of 1-hydroxybenztriazole dissolved in 120 ml. of dimethylformamide. The solution is cooled and treated with 5.6 ml. (40 mmol) of triethylamine and then with 8.64 g. of dicyclohexylcarbodiimide. The reaction is stirred with cooling for several hours and then allowed to come to room temperature in the ice bath. It is stirred overnight at room temperature and filtered. The filtrate is evaporated at reduced pressure and the residue dissolved in 400 ml. of ethyl acetate and washed three times with 5 percent sodium bicarbonate solution, dilute hydrochloric acid, saturated salt solution, dried over magnesium sulfate and evaporated. The residue is crystallized from ether-petroleum ether, re-dissolved in ether, filtered and crystallized by addition of petroleum ether; 12.88 g.; m.p. 65°-68° C.

Workup

  1. temperatureThe solution is cooled
  2. additiontreated with 5.6 ml
  3. temperaturewith cooling for several hours
  4. stirringIt is stirred overnight at room temperature
  5. filtrationfiltered
  6. customThe filtrate is evaporated at reduced pressure
  7. dissolutionthe residue dissolved in 400 ml
  8. washof ethyl acetate and washed three times with 5 percent sodium bicarbonate solution, dilute hydrochloric acid, saturated salt solution
  9. dry with materialdried over magnesium sulfate
  10. customevaporated
  11. customThe residue is crystallized from ether-petroleum ether
  12. dissolutionre-dissolved in ether
  13. filtrationfiltered
  14. customcrystallized by addition of petroleum ether

Sources & evidence

ORD record
ord-39e3a977a0054e818ba6701b7b6810d8
Source dataset
uspto-grants-1977_08
Patent number
US04043994

Reaction notes

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