4-Methylmorpholine → Acetylprolylalanylprolyl-2-azaalanyllactyllactic acid ethyl ester

HRID 461791Notes

Reaction equation

HRID 461791 reaction equation
[C:1]([N:4]1[CH2:23][CH2:22][CH2:21][C@H:5]1[C:6]([NH:8][C@H:9]([C:11]([N:13]1[CH2:20][CH2:19][CH2:18][C@H:14]1[C:15]([OH:17])=O)=[O:12])[CH3:10])=[O:7])(=[O:3])[CH3:2].CN1CCOCC1.ClC(OCC(C)C)=O.[CH2:39]([O:41][C:42](=[O:56])[C:43]([C:51](=[O:55])[CH:52]([CH3:54])[OH:53])([CH2:45][C:46](=[O:50])[N:47]([CH3:49])[NH2:48])[OH:44])[CH3:40]>C(#N)C>[CH2:39]([O:41][C:42](=[O:56])[C:43]([C:51](=[O:55])[CH:52]([CH3:54])[OH:53])([CH2:45][C:46](=[O:50])[N:47]([CH3:49])[NH:48][C:15](=[O:17])[C@@H:14]1[CH2:18][CH2:19][CH2:20][N:13]1[C:11](=[O:12])[C@H:9]([CH3:10])[NH:8][C:6](=[O:7])[C@@H:5]1[CH2:21][CH2:22][CH2:23][N:4]1[C:1](=[O:3])[CH3:2])[OH:44])[CH3:40]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 14503264AcetylprolylalanylprolineHCID 1317109832-Azaalanyllactyllactic acid ethyl ester

Product 1

HCID 131710984Acetylprolylalanylprolyl-2-azaalanyllactyllactic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

A mixture of 0.00185 moles of acetylprolylalanylproline and 0.20 ml of N-methylmorpholine in 20 ml of acetonitrile is cooled to -20° by means of a Dry Ice acetone bath. To this is added 0.28 ml of isobutyl chloroformate. After stirring for 10 minutes at -20° there is added 0.00185 moles of 2-azaalanyllactyllactic acid ethyl ester in 5 ml of acetonitrile. The reaction mixture is allowed to warm to room temperature after which it is stirred for 2 hours and then concentrated in vacuo. The residue is extracted between 50 ml of methylene chloride and 20 ml of cold 0.25 N hydrochloric acid. The acid layer is backwashed 2 times with 25 ml of methylene chloride. The organic extracts are combined, dried over sodium sulfate and concentrated in vacuo to give a glass. This residue is chromatographed on 75 gm of silica gel. Elution with methanol/methylene chloride (1-4%) gives pure acetylprolylalanylprolyl-2-azaalanyllactyllactic acid ethyl ester.

Workup

  1. temperatureis cooled to -20° by means of a Dry Ice acetone bath
  2. stirringis stirred for 2 hours
  3. concentrationconcentrated in vacuo
  4. extractionThe residue is extracted between 50 ml of methylene chloride and 20 ml of cold 0.25 N hydrochloric acid
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customto give a glass
  8. customThis residue is chromatographed on 75 gm of silica gel
  9. washElution with methanol/methylene chloride (1-4%)

Sources & evidence

ORD record
ord-f7875dceae1e4cde888a1844b64b8b2f
Source dataset
uspto-grants-1977_12
Patent number
US04064236

Reaction notes

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