Acetic Acid → Neotame

HRID 479012Notes

Reaction equation

HRID 479012 reaction equation
[CH3:1][O:2][C:3]([C@@H:5]([NH:13][C:14]([C@@H:16]([NH2:21])[CH2:17][C:18]([OH:20])=[O:19])=[O:15])[CH2:6][C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1)=[O:4].C(O)(=O)C.[CH3:26][C:27]([CH3:32])([CH3:31])[CH2:28][CH:29]=O>CO>[CH3:26][C:27]([CH2:28][CH2:29][NH:21][C@H:16]([C:14]([NH:13][C@H:5]([C:3]([O:2][CH3:1])=[O:4])[CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=[O:15])[CH2:17][C:18]([OH:20])=[O:19])([CH3:32])[CH3:31]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 763353,3-DimethylbutanalHCID 134601Aspartame

Product 1

HCID 9810996NeotameYield 97%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Aspartame (5.88 g), acetic acid (1.20 g) and methanol (100 ml) were charged to a hydrogenation vessel, followed by 3,3-dimethylbutyraldehyde (2.00 g). The vessel was pressure purged with nitrogen (4×), and 0.24 g of 4% palladium on carbon (containing 50% water) was added. After pressure purging the reactor with nitrogen (4×), followed by hydrogen (4×), the mixture was hydrogenated at 50 psig for 12 hours at room temperature. After completion of the reaction, the vessel was purged with nitrogen (4×). The catalyst was removed from the reaction mixture by filtration through powdered cellulose. Methanol (20 ml) was used to rinse the reaction vessel and the filter cake. The combined filtrate and wash was evaporated to dryness. The residue was stirred with 50 ml of deionized water and 50 ml of heptane for 4 hours at room temperature. The crystallized solid was isolated by filtration and washed with 20 ml heptane. The wet product was dried under vacuum at 40° C. to give 7.15 g of neotame (>97% by HPLC).

Workup

  1. custompurged with nitrogen (4×), and 0.24 g of 4% palladium on carbon (containing 50% water)
  2. additionwas added
  3. customAfter pressure purging the reactor with nitrogen (4×)
  4. customAfter completion of the reaction
  5. customthe vessel was purged with nitrogen (4×)
  6. customThe catalyst was removed from the reaction mixture by filtration through powdered cellulose
  7. washto rinse the reaction vessel
  8. washThe combined filtrate and wash
  9. customwas evaporated to dryness
  10. customThe crystallized solid was isolated by filtration
  11. washwashed with 20 ml heptane
  12. customThe wet product was dried under vacuum at 40° C.

Sources & evidence

ORD record
ord-fc100bc3fd4f4c9eb26d827c8e40453c
Source dataset
uspto-grants-2003_11
Patent number
US06642406B2

Reaction notes

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