Acetic Acid → Acetamidomalonic acid diethyl ester

HRID 2301700Notes

Reaction equation

HRID 2301700 reaction equation
[C:1]([OH:4])(=O)[CH3:2].[C:5]([O:13][CH2:14][CH3:15])(=[O:12])[CH2:6][C:7]([O:9][CH2:10][CH3:11])=[O:8].C(OC(=O)C)(=O)C.[N:23]([O-])=O.[Na+]>>[C:1]([NH:23][CH:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[C:5]([O:13][CH2:14][CH3:15])=[O:12])(=[O:4])[CH3:2]

Participants

5

Reactant 4

HCID 176Acetic AcidHCID 7761Diethyl MalonateHCID 7918Acetic AnhydrideHCID 23668193Sodium Nitrite

Product 1

HCID 14041Acetamidomalonic acid diethyl esterYield 85%

Conditions

Temperature
40 °C

Procedure

0.67 mol of acetic acid is fed into a mixture made from 0.38 mol of diethyl malonate, 1.14 mol of acetic anhydride and 0.5 mol of sodium nitrite, with stirring, at a temperature of 40° C., in such a way as to prevent the reaction temperature from exceeding 50° C. (metering time: about 3 hours). Stirring is continued for 4 hours at 50° C., followed by cooling to room temperature. Salts derived from the reaction are filtered off, and the salt is then washed with about 100 ml of methyl tert-butyl ether. The sodium acetate from the post precipitation is filtered off, and the mother liquor is mixed with 5 g of platinum/carbon (5%). The mixture is hydrogenated at a hydrogen pressure of 5 bar and a temperature of from 45 to 50° C.Hydrogen uptake ceases after about 4 hours. The mixture is cooled and the pressure released, and some of the solvent is removed by distillation in vacuo. After crystallization of the product the solid is isolated by filtration. This gives a yield of 85% of diethyl acetylaminomalonate.

Workup

  1. customfrom exceeding 50° C.
  2. custom(metering time: about 3 hours)
  3. stirringStirring
  4. temperatureby cooling to room temperature
  5. filtrationare filtered off
  6. washthe salt is then washed with about 100 ml of methyl tert-butyl ether
  7. customThe sodium acetate from the post precipitation
  8. filtrationis filtered off
  9. additionthe mother liquor is mixed with 5 g of platinum/carbon (5%)
  10. customof from 45 to 50° C
  11. waitHydrogen uptake ceases after about 4 hours
  12. temperatureThe mixture is cooled
  13. customsome of the solvent is removed by distillation in vacuo
  14. customAfter crystallization of the product the solid
  15. customis isolated by filtration

Sources & evidence

ORD record
ord-408388ee514c42fabf227a6e8dbd8609
Source dataset
uspto-grants-2002_12
Patent number
US06500980B1

Reaction notes

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