3,3-Dimethylbutanal → Neotame

HRID 479013Notes

Reaction equation

HRID 479013 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:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=[O:4].Cl.[CH3:23][C:24]([CH3:29])([CH3:28])[CH2:25][CH:26]=O.C(=O)([O-])O.[Na+]>CO.[Pd]>[CH3:23][C:24]([CH2:25][CH2:26][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])([CH3:29])[CH3:28]

Participants

6

Reactant 3

HCID 763353,3-DimethylbutanalHCID 134600L-Phenylalanine, L-alpha-aspartyl-, 2-methyl ester, hydrochloride (1:1)HCID 516892Sodium Bicarbonate

Product 1

HCID 9810996NeotameYield 90%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

Aspartame hydrochloride salt (10 mmol) and 3,3-dimethylbutyraldehyde (10 mmol) were dissolved in methanol (100 ml) in a hydrogenation vessel. Sodium hydrogen carbonate (NaHCO3, 12 mmol) and 5% palladium on carbon (100 mg) were added. The mixture was hydrogenated at 30-40 psi for 2 days at room temperature. After completion of the reaction, the catalyst was removed from the reaction mixture by filtration and washed with methanol (3×20 ml). The combined organic solvent was removed under reduced pressure below 40° C., and the residue was extracted using methylene chloride. The wet product was dried over sodium sulfate, and the solvent was removed in vacuo below 40° C. to give neotame in 90% yield.

Workup

  1. customAfter completion of the reaction
  2. customthe catalyst was removed from the reaction mixture by filtration
  3. washwashed with methanol (3×20 ml)
  4. customThe combined organic solvent was removed under reduced pressure below 40° C.
  5. extractionthe residue was extracted
  6. dry with materialThe wet product was dried over sodium sulfate
  7. customthe solvent was removed in vacuo below 40° C.

Sources & evidence

ORD record
ord-e6a892cbfb284f7fb1c7bdd54d106d49
Source dataset
uspto-grants-2003_11
Patent number
US06642406B2

Reaction notes

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