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

HRID 2060610

Reaction equation

HRID 2060610 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][CH2:1][C:2]1[C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=1.[Cl:15][C:4]1[CH:5]=[CH:6][C:7]([C:8]([O:10][CH3:11])=[O:9])=[C:2]([CH3:1])[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 (33.2 g, 199 mmol) was stirred in refluxing POCl3 (200 mL, 2146 mmol) for 3 hours. After cooling to room temperature, the reaction mixture poured into ice-water. The resulting dark solution was neutralized with solid sodium carbonate and the products extracted into ethyl acetate (3×). The combined organic extracts were washed with brine, dried over MgSO4 and concentrated in vacuo. Purification of the residue by flash chromatography (silica, 2-20% ethyl acetate/hexanes) gave methyl 2-(chloromethyl)pyridine-3-carboxylate as an orange oil and methyl 6-chloro-2-methylnicotinate as a light yellow oil.

Workup

  1. extractionthe products extracted into ethyl acetate (3×)
  2. washThe combined organic extracts were washed with brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customPurification of the residue by flash chromatography (silica, 2-20% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-12c228aa751a4984b6a94d508ca70b5f
Source dataset
uspto-grants-2012_10
Patent number
US08278335B2

Linked notes

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