Citric Acid → Z-Leu-Gly-OEt

HRID 1632392Notes

Reaction equation

HRID 1632392 reaction equation
CN1CCOCC1.[NH:8]([C:17]([O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:18])[C@H:9]([C:14]([OH:16])=O)[CH2:10][CH:11]([CH3:13])[CH3:12].ClC(OCC(C)C)=O.[NH2:35][CH2:36][C:37]([O:39][CH2:40][CH3:41])=[O:38].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCCC1.C(N(CC)CC)C.CN(C)C=O>[NH:8]([C:17]([O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:18])[C@H:9]([C:14]([NH:35][CH2:36][C:37]([O:39][CH2:40][CH3:41])=[O:38])=[O:16])[CH2:10][CH:11]([CH3:12])[CH3:13]

Participants

9

Reactant 5

HCID 311Citric AcidHCID 79724-MethylmorpholineHCID 12176Glycine ethyl esterHCID 62365Isobutyl chloroformateHCID 74840Leucine, N-carboxy-, N-benzyl ester, L-

Product 1

HCID 11810251Z-Leu-Gly-OEtYield 73.1%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
-15 °C

Procedure

1.86 Milliliters of N-methylmorpholine was dissolved in 60 ml of tetrahydrofuran and to this solution 4.85 g of Z-Leu-OH was added. The mixture was cooled to -15° C. and 2.41 ml of isobutyl chloroformate was added and then vigorously stirred for 30 seconds. To this reaction mixture, 40 ml of a dimethylformamide solution containing 2.54 g of H-Gly-OC2H5, and 2.56 ml of triethylamine were added and stirred for 1 minute. After the reaction mixture was warmed at 0° C. for 5 minutes, then at 40° C. for 2 minutes and was stirred at a room temperature for 15 minutes. Tetrahydrofuran and dimethylformamide were removed by distillation to obtain the residue, then 1M-citric acid was added to this residue and the crystals thus formed were collected by filtration. The crystals were washed with water until the filtrate become neutral, and the crystals were dried, reprecipitated from ethyl acetate-ether to obtain 4.68 g of Z-Leu-Gly-OC2H5.

Workup

  1. additionwas added
  2. additionwere added
  3. stirringstirred for 1 minute
  4. temperatureAfter the reaction mixture was warmed at 0° C. for 5 minutes
  5. waitat 40° C. for 2 minutes
  6. stirringwas stirred at a room temperature for 15 minutes
  7. customTetrahydrofuran and dimethylformamide were removed by distillation
  8. customto obtain the residue
  9. customthe crystals thus formed
  10. filtrationwere collected by filtration
  11. washThe crystals were washed with water until the filtrate
  12. customthe crystals were dried
  13. customreprecipitated from ethyl acetate-ether

Sources & evidence

ORD record
ord-910637f74c4a453bbb9f6780c4546c72
Source dataset
uspto-grants-1984_10
Patent number
US04474754

Reaction notes

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