Toluene → ethyl maleimidoacetate

HRID 406901Notes

Reaction equation

HRID 406901 reaction equation
Cl.[CH2:2]([O:4][C:5](=[O:8])[CH2:6][NH2:7])[CH3:3].[C:9]1(=O)[O:14][C:12](=[O:13])[CH:11]=[CH:10]1.C(N(CC)CC)C.C1(C)C=CC=CC=1>C(OC(=O)C)(=O)C.O>[C:9]1(=[O:14])[N:7]([CH2:6][C:5]([O:4][CH2:2][CH3:3])=[O:8])[C:12](=[O:13])[CH:11]=[CH:10]1

Participants

7

Reactant 4

HCID 1140TolueneHCID 7923Maleic AnhydrideHCID 8471TriethylamineHCID 2723640Glycine ethyl ester, hydrochloride

Product 1

HCID 6539156ethyl maleimidoacetateYield 45%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 7918Acetic AnhydrideSolvent2×

Procedure

In a separable flask, glycine ethyl ester hydrochloride (reagent grade) (279 g, 2 mol) was mixed into acetic anhydride (reagent grade) (800 ml). Then, to the mixture was added dropwise over 3 hours a solution of maleic anhydride (reagent grade) (196 g. 2 mol) in acetic anhydride (600 ml), with stirring at room temperature. After the dropwise addition, stirring was carried out for another 1 hour, and the resulting precipitate was collected by suction filtration, washed with ion-exchanged water, and dried. The product obtained (382 g), triethylamine (reagent grade) (404 g, 4 mol), and toluene (1200 ml) were charged into a separable flask equipped with a Dean-Stark trap. Then, the mixture was subjected to reaction at 120° C. for 2 hours with stirring. During the reaction, the water formed was removed with the Dean-Stark trap. After the reaction, toluene (300 ml) was added and the mixture was washed three times with ion-exchanged water. Then, the organic phase obtained was collected and subjected to removal of the toluene by evaporation using an evaporator and a vacuum dryer to give ethyl maleimidoacetate (165 g). (Yield: ca. 38%. The production of ethyl maleimidoacetate was verified by GPC measurement. The presence of ethyl maleimidoacetate was verified by 1H-NMR measurement using DMSO-d6. This compound is referred to hereinafter as Compound A4).

Workup

  1. additionAfter the dropwise addition
  2. stirringstirring
  3. filtrationthe resulting precipitate was collected by suction filtration
  4. washwashed with ion-exchanged water
  5. customdried
  6. additionwere charged into a separable flask
  7. customequipped with a Dean-Stark trap
  8. customThen, the mixture was subjected to reaction at 120° C. for 2 hours
  9. stirringwith stirring
  10. customDuring the reaction
  11. customwas removed with the Dean-Stark trap
  12. customAfter the reaction, toluene (300 ml)
  13. additionwas added
  14. washthe mixture was washed three times with ion-exchanged water
  15. customThen, the organic phase obtained
  16. customwas collected
  17. customsubjected to removal of the toluene by evaporation
  18. customan evaporator

Sources & evidence

ORD record
ord-97c1fb5ab02b45f8a0082930962edb08
Source dataset
uspto-grants-2014_06
Patent number
US08754178B2

Reaction notes

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