4-Methylmorpholine → HCID 131715032, compound

HRID 980442Notes

Reaction equation

HRID 980442 reaction equation
[NH:1]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C@H:2]([C:6]([NH:8][C@H:9]([C:19](O)=[O:20])[CH2:10][CH2:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:7])[CH:3]([CH3:5])[CH3:4].CN1CCOCC1.ClC(OCC(C)C)=O.[NH:44]1[CH2:79][CH2:78][CH2:77][C@H:45]1[C:46]([NH:48][C@H:49]([C:54]([N:56]1[CH2:76][CH2:75][CH2:74][C@H:57]1[C:58]([NH:60][C@H:61]([C:70]([O:72][CH3:73])=[O:71])[CH2:62][C:63]1[CH:68]=[CH:67][C:66]([OH:69])=[CH:65][CH:64]=1)=[O:59])=[O:55])[C@H:50]([CH2:52][CH3:53])[CH3:51])=[O:47]>O1CCCC1.CN(C)C=O>[NH:1]([C:22]([O:24][C:25]([CH3:26])([CH3:27])[CH3:28])=[O:23])[C@H:2]([C:6]([NH:8][C@H:9]([C:19]([N:44]1[CH2:79][CH2:78][CH2:77][C@H:45]1[C:46]([NH:48][C@H:49]([C:54]([N:56]1[CH2:76][CH2:75][CH2:74][C@H:57]1[C:58]([NH:60][C@H:61]([C:70]([O:72][CH3:73])=[O:71])[CH2:62][C:63]1[CH:68]=[CH:67][C:66]([OH:69])=[CH:65][CH:64]=1)=[O:59])=[O:55])[C@H:50]([CH2:52][CH3:53])[CH3:51])=[O:47])=[O:20])[CH2:10][CH2:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:7])[CH:3]([CH3:5])[CH3:4]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 131715033HCID 131715033, compoundHCID 131715034HCID 131715034, compound

Product 1

HCID 131715032HCID 131715032, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-15 °C

Procedure

0.8 g of Boc-Val-Glu(OBut)-OH (1.9 mmol) is dissolved in 5 cm3 of tetrahydrofuran cooled to -15° C. 0.21 cm3 of N-methylmorpholine (1.9 mmol) and 0.25 cm3 of isobutyl chloroformate are added in succession. After 2 minutes, the solution of Pro-Ile-Pro-Tyr-OMe in 5 cm3 of dimethylformamide, prepared earlier, is added. The reaction mixture is stirred for 1 hour at -15° C. and then for 2 hours at 20° C. The solvents are removed under reduced pressure. The 1.2 g of crude product obtained are purified by chromatography on silica gel by eluting with mixtures of ethyl acetate and petroleum ether (1-1; 7-2 and 8-2 by volume). The main fraction is purified by chromatography on silica gel by eluting with methylene chloride containing 3% of methanol (by volume). In this way, 0.6 g of Boc-Val-Glu(OBut)-Pro-Ile-Pro-Tyr-OMe is obtained, the properties of which are as follows:

Workup

  1. additionis added
  2. waitfor 2 hours at 20° C
  3. customThe solvents are removed under reduced pressure
  4. customThe 1.2 g of crude product obtained
  5. customare purified by chromatography on silica gel
  6. washby eluting with mixtures of ethyl acetate and petroleum ether (1-1; 7-2 and 8-2 by volume)
  7. customThe main fraction is purified by chromatography on silica gel
  8. washby eluting with methylene chloride containing 3% of methanol (by volume)

Sources & evidence

ORD record
ord-3db36f9a47fa42f88b47aa79eb4898f3
Source dataset
uspto-grants-1987_01
Patent number
US04637997

Reaction notes

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