Acetamidomalonic acid diethyl ester → Diethyl acetamido[(pyridin-4-yl)methyl]propanedioate

HRID 1883603Notes

Reaction equation

HRID 1883603 reaction equation
[OH-].[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].Br.Br[CH2:20][C:21]1[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=1>C(O)C>[C:3]([NH:6][C:7]([CH2:20][C:21]1[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=1)([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 14798Sodium Hydroxide2×HCID 127522194-(Bromomethyl)pyridine hbr

Product 1

HCID 13817909Diethyl acetamido[(pyridin-4-yl)methyl]propanedioateYield 82.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
20 °C

Procedure

To 750 mL of ethanol, about 9 g of sodium hydroxide is added dropwise, while stirring under an inert atmosphere. After the addition of sodium hydroxide, the temperature of reaction mixture is maintained at about 20° C., and 42 g of diethyl acetamidomalonate is slowly added then the mixture is stirred at a temperature of about 20° C. for 1 hour and 30 minutes. A suspension of 61.5 g of 4-bromomethyl-pyridine hydrobromide in 250 mL of ethanol is then quickly added and the resulting suspension is stirred at a temperature of about 20° C. for 18 hours. The reaction medium is then concentrated under reduced pressure (2 kPa) at a temperature of about 40° C. The residue is taken up in 200 mL of distilled water and is neutralized with 1N aqueous hydrochloric acid until the pH is equal to 7. The obtained suspension is cooled at a temperature of about 0° C., filtered and the insoluble material is washed with 2 times 50 mL of ice-cold water, then dried in an oven under reduced pressure (10 kPa) at a temperature of about 40° C. for 18 hours. Thus 49.4 g of diethyl 2-(acetylamino)-2-(4-pyridinylmethyl)malonate is obtained in the form of a white-pinkish solid. [Infrared spectrum CH2Cl2: 3409; 2895; 1741; 1681; 1603; 1496; 1302; 1198; 1057; 855; 557 and 524 cm−1].

Workup

  1. customthe temperature of reaction mixture
  2. stirringthe mixture is stirred at a temperature of about 20° C. for 1 hour and 30 minutes
  3. additionis then quickly added
  4. stirringthe resulting suspension is stirred at a temperature of about 20° C. for 18 hours
  5. concentrationThe reaction medium is then concentrated under reduced pressure (2 kPa) at a temperature of about 40° C
  6. temperatureThe obtained suspension is cooled at a temperature of about 0° C.
  7. filtrationfiltered
  8. washthe insoluble material is washed with 2 times 50 mL of ice-cold water
  9. customdried in an oven under reduced pressure (10 kPa) at a temperature of about 40° C. for 18 hours

Sources & evidence

ORD record
ord-ae88d9f375234516b64db0429aceac75
Source dataset
uspto-grants-2004_07
Patent number
US06762196B2

Reaction notes

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