p-Toluenesulfonic acid → Z-Gln-Trp-OBzl

HRID 1106301

Reaction equation

HRID 1106301 reaction equation
[NH2:1][C@H:2]([C:13]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:14])[CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][CH:5]=1.CC1C=CC(S(O)(=O)=O)=CC=1.[NH:34]([C:44]([O:46][CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)=[O:45])[C@H:35]([C:41](O)=[O:42])[CH2:36][CH2:37][C:38](=[O:40])[NH2:39].C1C2C3C(=O)N(O)C(=O)C3C1C=C2.C1CCC(N=C=NC2CCCCC2)CC1>C1COCC1>[NH:34]([C:44]([O:46][CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)=[O:45])[C@H:35]([C:41]([NH:1][C@H:2]([C:13]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:14])[CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][CH:5]=1)=[O:42])[CH2:36][CH2:37][C:38](=[O:40])[NH2:39]

Participants

7

Reactant 5

HCID 6101p-Toluenesulfonic acidHCID 10868DicyclohexylcarbodiimideHCID 75855L-Glutamine, N2-[(phenylmethoxy)carbonyl]-HCID 895293a,4,7,7a-Tetrahydro-2-hydroxy-4,7-methano-1H-isoindole-1,3(2H)-dioneHCID 7016092L-Tryptophan benzyl ester

Product 1

HCID 131712662Z-Gln-Trp-OBzl

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In 500 ml of THF is dissolved 50.0 g of H-Trp-OBzl. p-toluenesulfonate, and under ice-cooling, 15.4 ml of TEA, 28.0 g of Z-Gln-OH, 19.7 g of HONB and 22.7 g of DCC are added. The mixture is stirred for 15 hours. The precipitated DCU is filtered off, the filtrate concentrated and the residue dissolved in 300 ml of ethyl acetate. The solution is washed with saturated aqueous sodium hydrogen carbonate (150 ml×2), 10% aqueous citric acid (150 ml×2) and water (150 ml×2) in the order mentioned. The solvent is distilled off under reduced pressure, the residue dissolved in 300 ml of THF and the insolubles are filtered off. The filtrate is concentrated and precipitated with 500 ml of diethyl ether. The resultant powders are collected by filtration and recrystallized from acetonitrile. Yield 46.1 g (82.8%); [α]D23 +5.8°(c=1.0, DMF); Rf1 =0.60.

Workup

  1. filtrationThe precipitated DCU is filtered off
  2. concentrationthe filtrate concentrated
  3. dissolutionthe residue dissolved in 300 ml of ethyl acetate
  4. washThe solution is washed with saturated aqueous sodium hydrogen carbonate (150 ml×2), 10% aqueous citric acid (150 ml×2) and water (150 ml×2) in the order
  5. distillationThe solvent is distilled off under reduced pressure
  6. dissolutionthe residue dissolved in 300 ml of THF
  7. filtrationthe insolubles are filtered off
  8. concentrationThe filtrate is concentrated
  9. customprecipitated with 500 ml of diethyl ether
  10. filtrationThe resultant powders are collected by filtration
  11. customrecrystallized from acetonitrile

Sources & evidence

ORD record
ord-e7d34bca021c4b7791bce6297ca14fc3
Source dataset
uspto-grants-1982_01
Patent number
US04312943

Linked notes

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