Phosphorus oxychloride → Ethyl 4-chloro-6-methyl-2-(methylsulfanyl)pyrimidine-5-carboxylate

HRID 1744797Notes

Reaction equation

HRID 1744797 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]([S:14][CH3:15])[NH:5][C:6](=O)[C:7]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9].O=P(Cl)(Cl)[Cl:18]>>[Cl:18][C:6]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:2]([CH3:1])[N:3]=[C:4]([S:14][CH3:15])[N:5]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 135504073Ethyl 4-methyl-2-(methylthio)-6-oxo-1,6-dihydropyrimidine-5-carboxylate

Product 1

HCID 22225416Ethyl 4-chloro-6-methyl-2-(methylsulfanyl)pyrimidine-5-carboxylateYield 49%

Procedure

A mixture of compound C (60 g; 0.263 mol) and POCl3 (300 mL) was vigorously stirred under reflux temperature for 2 h. Then POCl3 was distilled off under vacuum, the crude solid triturated with water and ethyl acetate and filtered on a Celite pad. The filtrate was neutralized with sodium bicarbonate and extracted with ethyl acetate. The organic phase was washed with a saturated aqueous solution of sodium bicarbonate, washed with brine and dried over anhydrous sodium sulphate. After concentration the crude reaction mixture was purified by silica gel column chromatography (eluant: n-hexane/ethyl acetate=9/1) to yield compound D (31.8 g; 49%) as an orange oil.

Workup

  1. temperatureunder reflux temperature for 2 h
  2. distillationThen POCl3 was distilled off under vacuum
  3. customthe crude solid triturated with water and ethyl acetate
  4. filtrationfiltered on a Celite pad
  5. extractionextracted with ethyl acetate
  6. washThe organic phase was washed with a saturated aqueous solution of sodium bicarbonate
  7. washwashed with brine
  8. dry with materialdried over anhydrous sodium sulphate
  9. concentrationAfter concentration the crude
  10. customreaction mixture
  11. customwas purified by silica gel column chromatography (eluant: n-hexane/ethyl acetate=9/1)

Sources & evidence

ORD record
ord-654739b136fd44438b7337eb051e0299
Source dataset
uspto-grants-2006_03
Patent number
US07019002B2

Reaction notes

Loading…