L-Phenylalanine, methyl ester → L-Phenylalanine, L-alpha-aspartyl-, 2-methyl ester, hydrochloride (1:1)

HRID 236044Notes

Reaction equation

HRID 236044 reaction equation
[Cl:1]CC([NH:5][C@@H:6]1[C:11](=[O:12])[O:10][C:8](=[O:9])[CH2:7]1)=O.[NH2:13][C@H:14]([C:22]([O:24][CH3:25])=[O:23])[CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>ClC(Cl)C.C(O)(=O)C>[CH3:25][O:24][C:22]([C@@H:14]([NH:13][C:11]([C@@H:6]([NH2:5])[CH2:7][C:8]([OH:10])=[O:9])=[O:12])[CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:23].[ClH:1]

Participants

5

Reactant 2

HCID 736234L-Phenylalanine, methyl esterHCID 53642311Chloroacetyl l-aspartic acid anhydride

Product 1

HCID 134600L-Phenylalanine, L-alpha-aspartyl-, 2-methyl ester, hydrochloride (1:1)Yield 48%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
-5 °C

Procedure

150 Grams of N-chloroacetyl-L-aspartic acid anhydride are quickly added, at -5° C., to the solution of 140 grams of methyl L-phenylalaninate in 400 ml of dichloroethane plus 200 ml of acetic acid. The mixture is stirred for 1 hour at -5° C.; the temperature is then raised, in 2 hours, to 15° C., then, in 30 minutes, to 40° C. The dichloroethane is evaporated under vacuum; 500 ml of methanol and 60 grams of thiourea are added and the mixture is refluxed for 3 hours. After cooling to 20° C., 200 ml of methanol, containing 11% (by weight) of HCl, are added, the solution is cooled to 0° C. for 1 hour, filtered and evaporated to dryness in vacuo. The residue is crystallized from 600 ml of water containing 70 g of NaCl: a very pure aspartame hydrochloride is obtained, in a 48% yield.

Workup

  1. temperaturethe temperature is then raised, in 2 hours, to 15° C.
  2. waitin 30 minutes
  3. customto 40° C
  4. customThe dichloroethane is evaporated under vacuum
  5. addition500 ml of methanol and 60 grams of thiourea are added
  6. temperaturethe mixture is refluxed for 3 hours
  7. temperatureAfter cooling to 20° C.
  8. addition200 ml of methanol, containing 11% (by weight) of HCl
  9. additionare added
  10. temperaturethe solution is cooled to 0° C. for 1 hour
  11. filtrationfiltered
  12. customevaporated to dryness in vacuo
  13. customThe residue is crystallized from 600 ml of water containing 70 g of NaCl

Sources & evidence

ORD record
ord-47bb1c994bc54a1096b3d379686c6f2f
Source dataset
uspto-grants-1987_02
Patent number
US04642367

Reaction notes

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