Phosphorus trichloride → N-acetoacetyl-L-aspartyl-L-phenylalanine methyl ester

HRID 1583896Notes

Reaction equation

HRID 1583896 reaction equation
[C:1]([NH:7][C@H:8]([C:13]([O-:15])=O)[CH2:9][C:10]([O-:12])=[O:11])(=[O:6])[CH2:2][C:3]([CH3:5])=[O:4].[Na+].[Na+].P(Cl)(Cl)Cl.C(N[C@@H]1C(=O)OC(=O)C1)(=O)CC(C)=O.[CH3:36][O:37][C:38](=[O:48])[C@H:39]([CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[NH2:40]>O1CCOCC1.C(O)(=O)C.C(OCC)(=O)C>[CH3:36][O:37][C:38](=[O:48])[C@H:39]([CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[NH:40][C:13](=[O:15])[C@H:8]([CH2:9][C:10](=[O:11])[OH:12])[NH:7][C:1](=[O:6])[CH2:2][C:3]([CH3:5])=[O:4]

Participants

8

Reactant 4

HCID 24387Phosphorus trichlorideHCID 736234L-Phenylalanine, methyl esterHCID 13334674N-acetoacetyl-L-aspartic anhydrideHCID 86739332Disodium N-acetoacetylaspartate

Product 1

HCID 13334676N-acetoacetyl-L-aspartyl-L-phenylalanine methyl ester

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

Crude disodium N-acetoacetylaspartate, 28.51 parts, was stirred with 200 parts by volume of ethyl acetate and 11.7 parts by volume of acetic acid at 0°-5° C. under argon while 4.37 parts by volume of phosphorous trichloride was added dropwise. The resulting mixture was allowed to warm to ambient temperatures while stirring for 20 hours. To the resulting solution which contains N-acetoacetyl-L-aspartic anhydride was added dropwise over a 2 hour period 122 parts by volume of 0.9M L-phenylalanine methyl ester in dioxane. After continued stirring for 20 hours, the solvent was evaporated under vacuum at 35°-40° C. Toluene, 200 parts by volume, was added to the residue and the evaporation was repeated, giving crude N-acetoacetyl-L-aspartyl-L-phenylalanine methyl ester as a semi-solid yellow residue.

Workup

  1. additionwas added dropwise
  2. temperatureto warm to ambient temperatures
  3. stirringAfter continued stirring for 20 hours
  4. customthe solvent was evaporated under vacuum at 35°-40° C
  5. additionToluene, 200 parts by volume, was added to the residue
  6. customthe evaporation

Sources & evidence

ORD record
ord-6ab30196dcec42a59680382c5d2f7837
Source dataset
uspto-grants-1985_11
Patent number
US04555362

Reaction notes

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