4-Methylmorpholine → HCID 13419940, compound

HRID 1262876Notes

Reaction equation

HRID 1262876 reaction equation
CN1CCOCC1.C(Cl)(=O)C(C)(C)C.[C:15]([O:19][C:20]([NH:22][C@H:23]([C:36]([OH:38])=O)[CH2:24][C:25]1[CH:30]=[CH:29][C:28]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[CH:27][CH:26]=1)=[O:21])([CH3:18])([CH3:17])[CH3:16].[C:39]1([CH2:45][CH2:46][CH2:47][NH:48][C:49](=[O:56])[C@@H:50]([CH2:52][CH2:53][S:54][CH3:55])[NH2:51])[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1>O1CCCC1.C(OCC)(=O)C>[C:15]([O:19][C:20]([NH:22][C@H:23]([C:36]([NH:51][C@@H:50]([C:49]([NH:48][CH2:47][CH2:46][CH2:45][C:39]1[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=1)=[O:56])[CH2:52][CH2:53][S:54][CH3:55])=[O:38])[CH2:24][C:25]1[CH:30]=[CH:29][C:28]([O:31][C:32]([CH3:33])([CH3:35])[CH3:34])=[CH:27][CH:26]=1)=[O:21])([CH3:17])([CH3:18])[CH3:16]

Participants

7

Reactant 4

HCID 79724-Methylmorpholine2×HCID 62493Pivaloyl chlorideHCID 7017901Boc-Tyr(tBu)-OHHCID 13419937HCID 13419937, compound

Product 1

HCID 13419940HCID 13419940, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-20 °C

Procedure

N-methylmorpholine (485 mg.), then a solution of pivalyl chloride (579 mg.) in tetrahydrofuran (5 ml.), were added to a solution of N-(tert-butyloxycarbonyl)-O-(tert-butyl)-L-tyrosine in tetrahydrofuran (35 ml.) maintained at -20° C., and the mixture was stirred at that temperature for about 10 minutes. A solution of N-(3-phenylpropyl)-D-methioninamide (1.50 g.) and N-methylmorpholine (485 mg.) in tetrahydrofuran (60 ml.) was then added, and stirring was continued at -20° C. for two hours and then at room temperature overnight. Ethyl acetate (150 ml.) was added. The mixture was washed three times with saturated aqueous sodium bicarbonate, three times with aqueous citric acid (5%), twice with water and twice with saturated aqueous sodium chloride, dried over magnesium sulfate and concentrated under vacuum. Crystallization of the residue from ethyl acetate-hexane afforded as a white solid [N-(tert-butyloxycarbonyl)-O-(tert-butyl)-L-tyrosyl]-N-(3-phenylpropyl)-D-methioninamide (680 mg.; m.r. 158°-159° C.; [α]D25 +55.4°, c=1 methanol).

Workup

  1. stirringstirring
  2. waitwas continued at -20° C. for two hours
  3. customat room temperature
  4. customovernight
  5. washThe mixture was washed three times with saturated aqueous sodium bicarbonate, three times with aqueous citric acid (5%)
  6. dry with materialtwice with water and twice with saturated aqueous sodium chloride, dried over magnesium sulfate
  7. concentrationconcentrated under vacuum
  8. customCrystallization of the residue from ethyl acetate-hexane

Sources & evidence

ORD record
ord-f9bef31fd8a64ea68f7f1bfe49f4b899
Source dataset
uspto-grants-1984_06
Patent number
US04454120

Reaction notes

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