4-Methylmorpholine → N-t-butoxycarbonyl-L-methionyl-L-aspartyl-D-alanine amide

HRID 596803Notes

Reaction equation

HRID 596803 reaction equation
CN1CCOCC1.O.[NH2:9][C@H:10]([C:15]([NH:17][C@@H:18]([C:20]([NH2:22])=[O:21])[CH3:19])=[O:16])[CH2:11][C:12](=[O:14])[OH:13].Cl.O1CCOCC1.ClC1C=C(Cl)C(Cl)=CC=1[O:39][C:40](=O)[C@H:41]([CH2:50][CH2:51][S:52][CH3:53])[NH:42][C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44]>CN(C)C=O>[C:46]([O:45][C:43]([NH:42][C@H:41]([C:40]([NH:9][C@H:10]([C:15]([NH:17][C@@H:18]([C:20]([NH2:22])=[O:21])[CH3:19])=[O:16])[CH2:11][C:12](=[O:13])[OH:14])=[O:39])[CH2:50][CH2:51][S:52][CH3:53])=[O:44])([CH3:49])([CH3:48])[CH3:47]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 13670107N-t-butoxycarbonyl-L-methionine 2,4,5-trichlorophenyl esterHCID 204431481,4-Dioxane hydrochlorideHCID 22796342L-aspartyl-D-alanine amide monohydrate

Product 1

HCID 22796339N-t-butoxycarbonyl-L-methionyl-L-aspartyl-D-alanine amide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

14.5 Parts of N-methylmorpholine is added to a stirred solution of 14.33 parts of L-aspartyl-D-alanine amide monohydrate in 189 parts of dimethylformamide and 12.6 parts by volume of a 5.60 N HCl/dioxane solution. Then, 33.2 parts of N-t-butoxycarbonyl-L-methionine 2,4,5-trichlorophenyl ester is added and the resulting mixture stirred for about 18 hours at room temperature. The solvent is removed in vacuo and the resultant syrupy oil dissolved in ethyl acetate. To this solution is added 0.82 parts of N,N-diethylaminoethylamine and the resulting mixture is stirred for about 35 minutes. The mixture is then washed twice with 5% potassium hydrogen sulfate solution, dried over anhydrous sodium sulfate, and stripped under reduced pressure to a gummy residue. The gum is triturated with ethyl ether, to yield crystals which are filtered and dried to afford N-t-butoxycarbonyl-L-methionyl-L-aspartyl-D-alanine amide. This product melts at about 107-110° C., and is represented by the following formula.

Workup

  1. customThe solvent is removed in vacuo
  2. dissolutionthe resultant syrupy oil dissolved in ethyl acetate
  3. additionTo this solution is added 0.82 parts of N,N-diethylaminoethylamine
  4. stirringthe resulting mixture is stirred for about 35 minutes
  5. washThe mixture is then washed twice with 5% potassium hydrogen sulfate solution
  6. dry with materialdried over anhydrous sodium sulfate
  7. customThe gum is triturated with ethyl ether
  8. customto yield crystals which
  9. filtrationare filtered
  10. customdried

Sources & evidence

ORD record
ord-c28d8c01df9548f6ab15d390cbac8b58
Source dataset
uspto-grants-1977_03
Patent number
US04012367

Reaction notes

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