4-Methylmorpholine → HCID 54293522, compound

HRID 372775Notes

Reaction equation

HRID 372775 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:18]([NH:20][CH2:21][C:22]([NH:24][CH2:25][C:26](O)=[O:27])=[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.Cl.[CH2:45]([O:52][C:53](=[O:74])[C@H:54]([CH2:70][CH2:71][S:72][CH3:73])[NH:55][C:56](=[O:69])[C@H:57]([CH2:59][C:60]1[C:68]2[C:63](=[CH:64][CH:65]=[CH:66][CH:67]=2)[NH: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:74])[C@H:54]([CH2:70][CH2:71][S:72][CH3:73])[NH:55][C:56](=[O:69])[C@H:57]([CH2:59][C:60]1[C:68]2[C:63](=[CH:64][CH:65]=[CH:66][CH:67]=2)[NH:62][CH:61]=1)[NH:58][C:26](=[O:27])[CH2:25][NH:24][C:22](=[O:23])[CH2:21][NH:20][C:18](=[O:19])[C@H:9]([CH2:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=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 12821762N-(tert-Butoxycarbonyl)-L-tyrosylglycylglycineHCID 70619178HCID 70619178, compound

Product 1

HCID 54293522HCID 54293522, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
-15 °C

Procedure

10.0 Parts N-t-butoxycarbonyl-L-tyrosylglycylglycine and 2.4 parts N-methylmorpholine are dissolved in 125 parts dimethylformamide and cooled to -15° C. Then 3.8 parts isobutyl chloroformate is added dropwise over a 30 minute period while maintaining the temperature at -15° C. Then, a solution of 12.7 parts L-tryptophyl-L-methionine benzyl ester hydrochloride in 50 parts dimethylformamide is slowly added at -15° C. and the mixture is stirred at this temperature for 30 minutes. The cooling apparatus is removed and the mixture is stirred at ambient temperature for an additional 2 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-tyrosylglycylglycyl-L-tryptophyl-L-methionine benzyl ester.

Workup

  1. temperaturewhile maintaining the temperature at -15° C
  2. customThe cooling apparatus is removed
  3. stirringthe mixture is stirred at ambient temperature for an additional 2 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-a2fb4fad983446198b67d94d766add15
Source dataset
uspto-grants-1978_05
Patent number
US04092304

Reaction notes

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