Acetic Anhydride → L-aspartyl-L-phenylalanine methyl ester hydrochloride dihydrate

HRID 1583908

Reaction equation

HRID 1583908 reaction equation
C([O-])(=[O:3])C.[Mg+2].C([O-])(=[O:8])C.C(OC(=O)C)(=O)C.C([NH:23][C@H:24]([C:29](O)=[O:30])[CH2:25][C:26]([OH:28])=[O:27])(=O)CC(C)=O.[CH3:32][O:33][C:34](=[O:44])[C@H:35]([CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[NH2:36].[ClH:45].NO>C(O)(=O)C.O.C1(C)C=CC=CC=1>[OH2:3].[OH2:8].[ClH:45].[CH3:32][O:33][C:34](=[O:44])[C@H:35]([CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[NH:36][C:29](=[O:30])[C@H:24]([CH2:25][C:26](=[O:27])[OH:28])[NH2:23]

Participants

9

Reactant 5

HCID 7918Acetic AnhydrideHCID 8896Magnesium AcetateHCID 443297Hydroxyamine hydrochlorideHCID 736234L-Phenylalanine, methyl esterHCID 13334672N-acetoacetylaspartic acid

Product 1

HCID 13020137L-aspartyl-L-phenylalanine methyl ester hydrochloride dihydrate

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 1140TolueneSolvent2×

Conditions

Temperature
50 °C

Procedure

0.2 parts of magnesium acetate were dissolved in 11.4 parts by volume of acetic acid. To this solution was added 9.9 parts by volume of acetic anhydride, 120 parts by volume of toluene, and 21.72 parts of N-acetoacetylaspartic acid. The resulting mixture was heated at 50° C. under nitrogen for 1.5 hours, then cooled to 20°-25° C. A solution containing 17.92 parts L-phenylalanine methyl ester in 30 parts by volume of toluene was added dropwise over a 20 minute period and the mixture stirred overnight. 6.95 parts of hydroxylamine hydrochloride in 100 parts by volume of water was added and stirring was continued for 2.5 hours. The aqueous layer was separated, extracted four times with 50 parts by volume of methylene chloride and cooled to 5° C. 15 parts by volume of concentrated hydrochloric acid were added and the mixture stirred at 5° C. for 1.5 hours. The precipitate was collected on a filter and pulled dry overnight to give 25.93 parts of L-aspartyl-L-phenylalanine methyl ester hydrochloride dihydrate.

Workup

  1. temperaturecooled to 20°-25° C
  2. additionwas added dropwise over a 20 minute period
  3. stirringstirring
  4. waitwas continued for 2.5 hours
  5. customThe aqueous layer was separated
  6. extractionextracted four times with 50 parts by volume of methylene chloride
  7. temperaturecooled to 5° C
  8. addition15 parts by volume of concentrated hydrochloric acid were added
  9. stirringthe mixture stirred at 5° C. for 1.5 hours
  10. customThe precipitate was collected on
  11. filtrationa filter
  12. custompulled dry overnight

Sources & evidence

ORD record
ord-f5636cec203c43129979d2c2f1f39f39
Source dataset
uspto-grants-1985_11
Patent number
US04555362

Linked notes

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