Acetamidomalonic acid diethyl ester → HCID 10544484, compound

HRID 52812

Reaction equation

HRID 52812 reaction equation
[H-].[Na+].[C:3]([NH:6][CH:7]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[C:8]([O:10][CH2:11][CH3:12])=[O:9])(=[O:5])[CH3:4].[C:18]([O:21][CH2:22][CH2:23][CH2:24][CH2:25]Br)(=[O:20])[CH3:19]>CN(C)C=O>[C:3]([NH:6][C:7]([CH2:25][CH2:24][CH2:23][CH2:22][O:21][C:18](=[O:20])[CH3:19])([C:13]([O:15][CH2:16][CH3:17])=[O:14])[C:8]([O:10][CH2:11][CH3:12])=[O:9])(=[O:5])[CH3:4]

Participants

5

Reactant 3

HCID 14041Acetamidomalonic acid diethyl esterHCID 24758Sodium hydrideHCID 784911-Butanol, 4-bromo-, 1-acetate

Product 1

HCID 10544484HCID 10544484, compoundYield 98.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

A stirred suspension of 95% sodium hydride (60.8 g, 2.532 mol) in anhydrous dimethylformamide (500 ml) under an atmosphere of argon was cooled to 0° C. (ice bath). A solution of diethyl acetamidomalonate (500 g, 2.302 mol) in anhydrous dimethylformamide (1.2 l) was added over a period of 45 minutes while keeping the reaction temperature below 18° C. After the addition was complete, the turbid solution was gradually warmed to room temperature. After stirring for one hour at room temperature, 4-bromobutyl acetate (471.5 g, 2.417 mol) was added. The mixture was then stirred at 59°-60° C. for 18 hours. The resulting slurry was cooled to room temperature, quenched with absolute ethanol (40 ml) and glacial acetic acid (4 ml), stirred for about 15 minutes, poured into a 10% lithium chloride solution and extracted with ethyl acetate (2×3 l). The combined ethyl acetate extracts were washed with 10% lithium chloride (3×3 l), dried (anhydrous sodium sulfate), and evaporated in vacuo to give 750 g of title product as an oil.

Workup

  1. customthe reaction temperature below 18° C
  2. additionAfter the addition
  3. temperaturethe turbid solution was gradually warmed to room temperature
  4. stirringThe mixture was then stirred at 59°-60° C. for 18 hours
  5. temperatureThe resulting slurry was cooled to room temperature
  6. customquenched with absolute ethanol (40 ml) and glacial acetic acid (4 ml)
  7. stirringstirred for about 15 minutes
  8. additionpoured into a 10% lithium chloride solution
  9. extractionextracted with ethyl acetate (2×3 l)
  10. washThe combined ethyl acetate extracts were washed with 10% lithium chloride (3×3 l)
  11. dry with materialdried (anhydrous sodium sulfate)
  12. customevaporated in vacuo

Sources & evidence

ORD record
ord-c18b93b4b3584bbda3629d1892b74815
Source dataset
uspto-grants-1997_04
Patent number
US05616775

Linked notes

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