Phosphorus oxychloride → Methyl 2-(chloromethyl)pyridine-3-carboxylate

HRID 2277613Notes

Reaction equation

HRID 2277613 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:6]([CH3:12])=[N+:7]([O-])[CH:8]=[CH:9][CH:10]=1)=[O:4].O=P(Cl)(Cl)[Cl:15]>>[Cl:15][CH2:12][C:6]1[N:7]=[CH:8][CH:9]=[CH:10][C:5]=1[C:3]([O:2][CH3:1])=[O:4]

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 20163965Methyl 2-methylnicotinate 1-oxide

Product 1

HCID 19081344Methyl 2-(chloromethyl)pyridine-3-carboxylateYield 30.8%

Procedure

The crude 3-(methoxycarbonyl)-2-methylpyridine-1-oxide (35 g, 210 mmol) was added in small portion to POCl3 (300 g) at room temperature. After the addition, the reaction mixture was refluxed for 3 hours before it was concentrated in vacuo. The residue was poured into ice-water, neutralized with aq. NaHCO3 solution and extracted with AcOEt (125 mL×3). The combined organic layers were washed with brine, dried over anhy. NazSO4, filtered, and concentrated in vacuo to afford a crude product which was then purified by column chromatography to give title compound (12 g, yield 30%).

Workup

  1. additionAfter the addition
  2. temperaturethe reaction mixture was refluxed for 3 hours before it
  3. concentrationwas concentrated in vacuo
  4. additionThe residue was poured into ice-water
  5. extractionextracted with AcOEt (125 mL×3)
  6. washThe combined organic layers were washed with brine
  7. customdried over anhy
  8. filtrationNazSO4, filtered
  9. concentrationconcentrated in vacuo
  10. customto afford a crude product which
  11. customwas then purified by column chromatography

Sources & evidence

ORD record
ord-33d9fe326e4d4b27b8b47448ca2f3aaf
Source dataset
uspto-grants-2015_09
Patent number
US09133158B2

Reaction notes

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