Methanol → Ethyl 2-(6-Chloro-4-pyrimidinyl)acetate

HRID 1458669Notes

Reaction equation

HRID 1458669 reaction equation
[H-].[Na+].[C:3]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:4][C:5]([CH3:7])=O.[Cl:12][C:13]1C=C(Cl)[N:16]=[CH:15][N:14]=1.CO>O1CCOCC1>[Cl:12][C:13]1[CH:7]=[C:5]([CH2:4][C:3]([O:9][CH2:10][CH3:11])=[O:8])[N:16]=[CH:15][N:14]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 8868Ethyl AcetoacetateHCID 24758Sodium hydrideHCID 709434,6-Dichloropyrimidine

Product 1

HCID 54342093Ethyl 2-(6-Chloro-4-pyrimidinyl)acetate

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
50 °C

Procedure

2.7 g (50 mmol) of sodium hydride (80% dispersion in oil) were placed in 100 ml of dry dioxane, and 11.7 g (90 mmol) of ethyl acetoacetate were added dropwise. The mixture was then stirred at 50° C. for 1 hour. After cooling to room temperature, a solution of 4.5 g (30 mmol) of 4,6-dichloropyrimidine in 50 ml of dioxane was added dropwise. After heating at reflux for 6 hours the mixture was cooled to room temperature, 10 ml of methanol were added dropwise in order to destroy superfluous sodium hydride, and the mixture was concentrated. The residue was taken up in water and brought to a pH of 3 to 4 with conc. hydrochloric acid. After extractive stirring with toluene, the organic phase was dried and concentrated. Chromatography on silica gel left 1.8 g (30% of theory) of a colorless oil.

Workup

  1. temperatureAfter cooling to room temperature
  2. temperatureAfter heating
  3. temperatureat reflux for 6 hours the mixture
  4. temperaturewas cooled to room temperature
  5. customto destroy superfluous sodium hydride
  6. concentrationthe mixture was concentrated
  7. stirringAfter extractive stirring with toluene
  8. customthe organic phase was dried
  9. concentrationconcentrated
  10. waitChromatography on silica gel left 1.8 g (30% of theory) of a colorless oil

Sources & evidence

ORD record
ord-d76f463cbef24e9a8eea25876e3b2efc
Source dataset
uspto-grants-1998_12
Patent number
US05852023

Reaction notes

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