Sodium Carbonate → Methyl 2-(chloromethyl)pyridine-3-carboxylate

HRID 385950

Reaction equation

HRID 385950 reaction equation
[CH3:1][C:2]1[C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=[CH:4][N+:3]=1[O-].O=P(Cl)(Cl)[Cl:15].C([O-])([O-])=O.[Na+].[Na+]>>[Cl:15][C:4]1[N:3]=[C:2]([CH3:1])[C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=1.[Cl:15][CH2:1][C:2]1[C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 24813Phosphorus oxychlorideHCID 20163965Methyl 2-methylnicotinate 1-oxide

Product 2

HCID 19081344Methyl 2-(chloromethyl)pyridine-3-carboxylateHCID 59650775Methyl 6-chloro-2-methylpyridine-3-carboxylate

Procedure

Methyl 2-methylpyridine-3-carboxylate 1-oxide (2.93 g, 17.53 mmol) was taken up in POCl3 (17 mL, 182 mmol) and heated to reflux for 3 hours. The mixture was then cooled to room temperature and poured into ice-water. The resulting dark solution was neutralised with solid Na2CO3 and the products extracted into EtOAc (×3). The combined organic extracts were washed with brine, dried over MgSO4, filtered, and concentrated in vacuo. Purification of the residue by silica gel chromatography (2-30% EtOAc-hexanes) gave methyl 6-chloro-2-methylpyridine-3-carboxylate as a pale yellow oil (A) and methyl 2-(chloromethyl)pyridine-3-carboxylate (B) as an orange oil.

Workup

  1. temperatureheated
  2. temperatureto reflux for 3 hours
  3. extractionthe products extracted into EtOAc (×3)
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification of the residue by silica gel chromatography (2-30% EtOAc-hexanes)

Sources & evidence

ORD record
ord-284d896ff94d4878a6f9357d2bb47da7
Source dataset
uspto-grants-2013_02
Patent number
US08367706B2

Linked notes

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