Phosphorus oxychloride → 4-Methoxymethyl-5-methyl-6-chloropyrimidine

HRID 2401214Notes

Reaction equation

HRID 2401214 reaction equation
[CH3:1][C:2]1[C:3](O)=[N:4][CH:5]=[N:6][C:7]=1[CH2:8][O:9][CH3:10].P(Cl)(Cl)([Cl:14])=O>C(Cl)Cl>[Cl:14][C:3]1[C:2]([CH3:1])=[C:7]([CH2:8][O:9][CH3:10])[N:6]=[CH:5][N:4]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178494687HCID 178494687, compound2×

Product 1

HCID 143061604-Methoxymethyl-5-methyl-6-chloropyrimidineYield 91%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

5-Methyl-6-[(methyloxy)methyl]-4-pyrimidinol (Intermediate 48, 2.10 g, 13.62 mmol) was dissolved in DCM (20 ml), treated with phosphorus oxychloride (12.04 ml, 129 mmol) and the resulting mixture was heated under reflux for 3 hours, allowed to cool to room temperature and left to stand overnight. The solvent was removed under reduced pressure, the residue taken up in ice water and the pH was adjusted to 7 using aqueous 2M sodium hydroxide solution. The mixture was extracted with chloroform (×3) and the chloroform layers were separated, combined, dried under magnesium sulfate and evaporated under reduced pressure. The residue was purified by SP4 Biotage column chromatography eluting with a gradient of 0-50% ethyl acetate and iso-hexane. Product containing fractions were combined and evaporated under reduced pressure to give the title compound as a yellow oil (2.14 g);

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureunder reflux for 3 hours
  3. waitleft
  4. customThe solvent was removed under reduced pressure
  5. extractionThe mixture was extracted with chloroform (×3)
  6. customthe chloroform layers were separated
  7. customdried under magnesium sulfate
  8. customevaporated under reduced pressure
  9. customThe residue was purified by SP4 Biotage column chromatography
  10. washeluting with a gradient of 0-50% ethyl acetate and iso-hexane
  11. additionProduct containing fractions
  12. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-e792e26784f444fd86ac0d894dc23d39
Source dataset
uspto-grants-2014_08
Patent number
US08796283B2

Reaction notes

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