Dimethylformamide → Aspartame

HRID 1605181ノート

反応式

HRID 1605181 の反応式
CC1(OC(N[C@@H]2C(=O)OC(=O)C2)=O)CCC1.Cl.COC(=O)[C@H](CC1C=CC=CC=1)N.CN(C)C=O.[CH3:36][O:37][C:38](=[O:64])[C@H:39]([CH2:57][C:58]1[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=1)[NH:40][C:41](=[O:56])[C@H:42]([CH2:52][C:53](=[O:55])[OH:54])[NH:43]C(OC1(C)CCC1)=O>C(N(CC)CC)C>[CH3:36][O:37][C:38](=[O:64])[C@H:39]([CH2:57][C:58]1[CH:59]=[CH:60][CH:61]=[CH:62][CH:63]=1)[NH:40][C:41](=[O:56])[C@H:42]([CH2:52][C:53](=[O:54])[OH:55])[NH2:43]

参加物

6

反応物 4

HCID 6228DimethylformamideHCID 75736Methyl L-phenylalaninate hydrochlorideHCID 22788822N-(1-methylcyclobutyloxycarbonyl) aspartyl-phenylalanine methyl esterHCID 54330780N-(1-Methylcyclobutyloxycarbonyl)-Aspartic Anhydride

生成物 1

HCID 134601Aspartame

試薬・触媒・溶媒 1

HCID 8471Triethylamine溶媒

反応条件

温度
20 °C

実験手順

Coupling of N-(1-methylcyclobutyloxycarbonyl) aspartic anhydride with phenylalanine methyl ester hydrochloride is carried out in an organic solvent, for example dimethylformamide in the presence of an amine such as triethylamine. The reaction is stirred for several hours at a temperature of about 20°C. Upon completion of the coupling reaction the solvent is removed and the residue dissolved in ethyl acetate. Extraction with acid and removal of the solvent affords a mixture of α and β N-(1-methylcyclobutyloxycarbonyl) aspartyl-phenylalanine methyl ester. The blocking group is removed by stirring the protected dipeptide ester in anhydrous hydrofluoric acid at 0°C. The α-isomer of aspartyl-phenylalanine methyl ester is isolated by treating an aqueous mixture of the α- and β- isomers with β-phenylpropionic acid at a pH of from 3-5. The α-aspartyl phenylalanine methyl ester β-phenylpropionic adduct precipitates out of the solution. The resulting adduct is readily decomposed by treatment with acid to produce α-aspartyl phenylalanine methyl ester.

後処理

  1. customUpon completion of the coupling reaction the solvent
  2. customis removed
  3. dissolutionthe residue dissolved in ethyl acetate
  4. extractionExtraction
  5. customwith acid and removal of the solvent
  6. customaffords
  7. customThe blocking group is removed
  8. stirringby stirring the protected dipeptide ester in anhydrous hydrofluoric acid at 0°C

出典と根拠

ORDレコード
ord-8ffdf17891074a63a758b3cbbb586feb
出典データセット
uspto-grants-1976_04
特許番号
US03948971

反応ノート

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