4-Methylmorpholine → Z-N-Me-Val-N-Me-Tyr(3-tBu)-NH2

HRID 1383742Notes

Reaction equation

HRID 1383742 reaction equation
[C:1]([N:11]([CH3:36])[C@H:12]([C:16]([N:18]([CH3:35])[C@H:19]([C:32](O)=[O:33])[CH2:20][C:21]1[CH:26]=[CH:25][C:24]([OH:27])=[C:23]([C:28]([CH3:31])([CH3:30])[CH3:29])[CH:22]=1)=[O:17])[CH:13]([CH3:15])[CH3:14])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].C[N:38]1CCOCC1>C1COCC1.ClC(OCC)=O>[C:1]([N:11]([CH3:36])[C@H:12]([C:16]([N:18]([CH3:35])[C@H:19]([C:32]([NH2:38])=[O:33])[CH2:20][C:21]1[CH:26]=[CH:25][C:24]([OH:27])=[C:23]([C:28]([CH3:29])([CH3:31])[CH3:30])[CH:22]=1)=[O:17])[CH:13]([CH3:14])[CH3:15])([O:3][CH2:4][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1)=[O:2]

Participants

5

Reactant 2

HCID 79724-MethylmorpholineHCID 131722750Z-N-Me-Val-N-Me-Tyr(3-tBu)-OH

Product 1

HCID 131722751Z-N-Me-Val-N-Me-Tyr(3-tBu)-NH2

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 10928Ethyl chloroformateSolvent

Procedure

To a solution of 1.96 g of Z-N-Me-Val-N-Me-Tyr(3-tBu)-OMe in 1,4-dioxane (40 ml), 2 N NaOH (5 ml) was added at room temperature and the mixture was stirred for 2 hours. The reaction mixture was adjusted to pH 3 with dilute hydrochloric acid and extracted with ethyl acetate. The extract was washed with saturated brine and the organic layer was dried with sodium sulfate. The solvent was distilled off under reduced pressure to give Z-N-Me-Val-N-Me-Tyr(3-tBu)-OH. To a solution of this Z-N-Me-Val-N-Me-Tyr(3-tBu)-OH in THF (20 ml), ethyl chloroformate (0.40 ml) and NMM (0.46 ml) were added under cooling with ice and the mixture was stirred for 15 minutes. Subsequently, ammonia gas was bubbled into the reaction mixture for 5 minutes. The solvent was distilled off under reduced pressure and the precipitating salt was filtered off and washed with ethyl acetate. The solvent was distilled off under reduced pressure and the resulting residue was subjected to silica gel column chromatography (eluting solvent; n-hexane:ethyl acetate=2:3) to give Z-N-Me-Val-N-Me-Tyr(3-tBu)-NH2 in the amount of 1.17 g (61%).

Workup

  1. temperatureunder cooling with ice
  2. customSubsequently, ammonia gas was bubbled into the reaction mixture for 5 minutes
  3. distillationThe solvent was distilled off under reduced pressure
  4. filtrationthe precipitating salt was filtered off
  5. washwashed with ethyl acetate
  6. distillationThe solvent was distilled off under reduced pressure
  7. washthe resulting residue was subjected to silica gel column chromatography (eluting solvent; n-hexane:ethyl acetate=2:3)

Sources & evidence

ORD record
ord-6c162120214b404eaacf787832fd716b
Source dataset
uspto-grants-2001_07
Patent number
US06255285B1

Reaction notes

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