4-Methylmorpholine → HCID 54262973, compound

HRID 436957Notes

Reaction equation

HRID 436957 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:18]([NH:20][CH2:21][C:22]([NH:24][C@H:25]([C:27](O)=[O:28])[CH3:26])=[O:23])=[O:19])[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.ClC(OCC(C)C)=O.[CH2:45]([O:52][C:53](=[O:71])[C@H:54]([CH2:67][CH:68]([CH3:70])[CH3:69])[NH:55][C:56](=[O:66])[C@H:57]([CH2:59][C:60]1[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=1)[NH2:58])[C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1>CN(C)C=O.O>[CH2:45]([O:52][C:53](=[O:71])[C@H:54]([CH2:67][CH:68]([CH3:69])[CH3:70])[NH:55][C:56](=[O:66])[C@H:57]([CH2:59][C:60]1[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=1)[NH:58][C:27](=[O:28])[C@H:25]([CH3:26])[NH:24][C:22](=[O:23])[CH2:21][NH:20][C:18](=[O:19])[C@H:9]([CH2:10][C:11]1[CH:12]=[CH:13][C:14]([OH:17])=[CH:15][CH:16]=1)[NH:8][C:6]([O:5][C:1]([CH3:3])([CH3:4])[CH3:2])=[O:7])[C:46]1[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 11783563HCID 11783563, compoundHCID 53837274HCID 53837274, compound

Product 1

HCID 54262973HCID 54262973, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
-15 °C

Procedure

14.0 Parts N-t-butoxycarbonyl-L-tyrosylglycyl-L-alanine and 3.5 parts N-methylmorpholine are dissolved in 200 parts dimethylformamide and cooled to -15° C. Then, 5.2 parts isobutyl chloroformate is added dropwise over a 30 minute period while maintaining the temperature at -15° C. Then, a solution of 9.8 parts L-phenylalanyl-L-leucine benzyl ester in 50 parts dimethylformamide is slowly added at -15° C., and the mixture stirred at this temperature for 30 minutes. The cooling apparatus is removed and the mixture stirred at ambient temperatures for an additional two hours. The product is isolated by diluting the reaction mixture with 10 volumes water and extracting with ethyl acetate. The ethyl acetate extracts are combined, dried over anhydrous sodium sulfate and stripped to dryness under reduced pressure. Purification of the residue by low pressure column chromatography affords N-t-butoxycarbonyl-L-tyrosylglycyl-L-alanyl-L-phenylalanyl-L-leucine benzyl ester.

Workup

  1. temperaturewhile maintaining the temperature at -15° C
  2. customThe cooling apparatus is removed
  3. stirringthe mixture stirred at ambient temperatures for an additional two hours
  4. customThe product is isolated
  5. extractionextracting with ethyl acetate
  6. dry with materialdried over anhydrous sodium sulfate
  7. customPurification of the residue by low pressure column chromatography

Sources & evidence

ORD record
ord-60a0cd2c0a3642a1b22a57357cfab0e7
Source dataset
uspto-grants-1977_06
Patent number
US04028319

Reaction notes

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