p-Toluenesulfonic acid → HCID 178427578, compound

HRID 647396Notes

Reaction equation

HRID 647396 reaction equation
[NH:1]([C:23]([O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:24])[C@H:2]([C:20](O)=[O:21])[CH2:3][CH2:4][CH2:5][NH:6][C:7](=[NH:19])[NH:8][S:9]([C:12]1[CH:18]=[CH:17][C:15]([CH3:16])=[CH:14][CH:13]=1)(=[O:11])=[O:10].CN1CCOCC1.ClC(OCC)=O.S(O)(C1C=CC(C)=CC=1)(=O)=O.[NH2:57][C@H:58]([C:63]([O:65][CH2:66][C:67]1[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=1)=[O:64])[CH2:59][CH:60]([CH3:62])[CH3:61]>O1CCCC1.CN(C)C=O>[NH:1]([C:23]([O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:24])[C@H:2]([C:20]([NH:57][C@H:58]([C:63]([O:65][CH2:66][C:67]1[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=1)=[O:64])[CH2:59][CH:60]([CH3:62])[CH3:61])=[O:21])[CH2:3][CH2:4][CH2:5][NH:6][C:7](=[NH:19])[NH:8][S:9]([C:12]1[CH:18]=[CH:17][C:15]([CH3:16])=[CH:14][CH:13]=1)(=[O:11])=[O:10]

Participants

8

Reactant 5

HCID 6101p-Toluenesulfonic acidHCID 79724-Methylmorpholine2×HCID 10928Ethyl chloroformateHCID 6451313Benzyl L-leucinateHCID 178427582HCID 178427582, compound

Product 1

HCID 178427578HCID 178427578, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-5 °C

Procedure

In 500 ml of tetrahydrofuran is dissolved 46.2 g (100 millimoles) of Z-Arg(Tos)-OH, and 11 ml of N-methylmorpholine is added to the solution and the mixture is stirred at -5° C. for 5 minutes. Then, 9.6 ml of ethyl chloroformate is added to the mixture, and a cooled solution of 39.4 g (100 millimoles) of Tos-OH.H-Leu-OBzl and 11 ml of N-methylmorpholine in dimethylformamide is added to the above mixture. The resulting mixture is stirred at -5° to 0° C. for 4 hours and concentrated under reduced pressure. The residue is dissolved in 700 ml of ethyl acetate, and the solution is washed with 0.1 N aqueous hydrochloric acid, 1 N aqueous NaHCO3 and water and concentrated under reduced pressure. Ether is added to the residue and the formed precipitate is recovered by filtration to obtain 58 g of intended Z-Arg(Tos)-Leu-OBzl (the yield being 87%).

Workup

  1. additionis added to the solution
  2. stirringThe resulting mixture is stirred at -5° to 0° C. for 4 hours
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe residue is dissolved in 700 ml of ethyl acetate
  5. washthe solution is washed with 0.1 N aqueous hydrochloric acid, 1 N aqueous NaHCO3 and water
  6. concentrationconcentrated under reduced pressure
  7. additionEther is added to the residue
  8. filtrationthe formed precipitate is recovered by filtration

Sources & evidence

ORD record
ord-3c0c0bd13afc4c36a2b8c050e6387102
Source dataset
uspto-grants-1983_10
Patent number
US04407745

Reaction notes

Loading…