Phosphorus oxychloride → Ethyl 4-chloro-2-(pyridin-4-yl)pyrimidine-5-carboxylate

HRID 1005974Notes

Reaction equation

HRID 1005974 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:7](O)=[N:8][C:9]([C:12]2[CH:17]=[CH:16][N:15]=[CH:14][CH:13]=2)=[N:10][CH:11]=1)=[O:5])[CH3:2].C([O-])(O)=O.[Na+].O=P(Cl)(Cl)[Cl:26]>>[CH2:1]([O:3][C:4]([C:6]1[C:7]([Cl:26])=[N:8][C:9]([C:12]2[CH:17]=[CH:16][N:15]=[CH:14][CH:13]=2)=[N:10][CH:11]=1)=[O:5])[CH3:2]

Participants

4

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 178469750HCID 178469750, compound

Product 1

HCID 24903915Ethyl 4-chloro-2-(pyridin-4-yl)pyrimidine-5-carboxylateYield 84%

Procedure

A suspension of 4.78 g (19.5 mmol) 4-hydroxy-2-pyridin-4-yl-pyrimidine-5-carboxylic acid ethyl ester in 20 ml POCl3 was heated at reflux for 1 h. The solution was cooled to RT and poured into 100 ml ice-water. The pH of the solution was adjusted to 8 with sat.NaHCO3-solution. The water-phase was extracted three times with 80 ml CH2Cl2. The combined organic phases were dried (MgSO4), filtered and evaporated. The residue was purified by chromatography (SiO2, CH2Cl2/MeOH 40:1) to give 4.34 g (84%) 4-chloro-2-pyridin-4-yl-pyrimidine-5-carboxylic acid ethyl ester as a yellow solid, MS (EI): 263.1 (M+).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 1 h
  3. extractionThe water-phase was extracted three times with 80 ml CH2Cl2
  4. dry with materialThe combined organic phases were dried (MgSO4)
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by chromatography (SiO2, CH2Cl2/MeOH 40:1)

Sources & evidence

ORD record
ord-cd99045c4859497297682167d58efbbe
Source dataset
uspto-grants-2004_09
Patent number
US06787539B2

Reaction notes

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