4-Methylmorpholine → HCID 178465172, compound

HRID 1279186

Reaction equation

HRID 1279186 reaction equation
[NH2:1][C@H:2]([C:7]([NH:9][C@H:10]([C:28]([N:30]1[CH2:39][CH2:38][CH2:37][C@H:31]1[C:32]([NH:34][CH2:35][CH3:36])=[O:33])=[O:29])[CH2:11][CH2:12][CH2:13][NH:14][C:15](=[NH:27])[NH:16][S:17]([C:20]1[CH:26]=[CH:25][C:23]([CH3:24])=[CH:22][CH:21]=1)(=[O:19])=[O:18])=[O:8])[CH2:3][CH:4]([CH3:6])[CH3:5].CN1CCOCC1.ON1C(=O)CCC1=O.CCN=C=NCCCN(C)C.[NH:66]([C:75]([O:77][C:78]([CH3:81])([CH3:80])[CH3:79])=[O:76])[C@@H:67]([C:72](O)=[O:73])[CH2:68][CH:69]([CH3:71])[CH3:70]>CN(C=O)C.C1COCC1>[NH:66]([C:75]([O:77][C:78]([CH3:80])([CH3:79])[CH3:81])=[O:76])[C@@H:67]([C:72]([NH:1][C@H:2]([C:7]([NH:9][C@H:10]([C:28]([N:30]1[CH2:39][CH2:38][CH2:37][C@H:31]1[C:32]([NH:34][CH2:35][CH3:36])=[O:33])=[O:29])[CH2:11][CH2:12][CH2:13][NH:14][C:15](=[NH:27])[NH:16][S:17]([C:20]1[CH:21]=[CH:22][C:23]([CH3:24])=[CH:25][CH:26]=1)(=[O:18])=[O:19])=[O:8])[CH2:3][CH:4]([CH3:6])[CH3:5])=[O:73])[CH2:68][CH:69]([CH3:71])[CH3:70]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 80170N-HydroxysuccinimideHCID 637604tert-Butoxycarbonyl-D-leucineHCID 178465175HCID 178465175, compound

Product 1

HCID 178465172HCID 178465172, compoundYield 92.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

H-Leu-Arg(Tos)-Pro-NHEt was dissolved in 80 mL of DMF and 200 mL of THF. With cooling the solution was neutralized with N-methylmorpholine. To the solution, a solution in which 8.86 g of Boc-D-Leu-OH and 23.02 g of HOSu were dissolved in 200 mL of THF, and 36.4 mL of WSC were added. Next the mixture was stirred at 0° C. for 5 minutes and at room temperature overnight. After confirmation with ninhidrin, the reaction mixture was concentrated under reduced pressure. To the residue, 500 mL of water was added, then the mixture was extracted 5 times with 200 mL of n-butanol and washed five times with water. The n-butanol layer was concentrated under reduced pressure, then the residue was solidified by treatment with ether. Thus 21.5 g of Boc-D-Leu-Leu-Arg(Tos)-Pro-NHEt (92.1% yield) was obtained.

Workup

  1. temperatureWith cooling the solution
  2. concentrationAfter confirmation with ninhidrin, the reaction mixture was concentrated under reduced pressure
  3. additionTo the residue, 500 mL of water was added
  4. extractionthe mixture was extracted 5 times with 200 mL of n-butanol
  5. washwashed five times with water
  6. concentrationThe n-butanol layer was concentrated under reduced pressure

Sources & evidence

ORD record
ord-dbb7accad3824ede81c12eda69c1e149
Source dataset
uspto-grants-2002_09
Patent number
US06448031B1

Linked notes

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