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

HRID 1032819Notes

Reaction equation

HRID 1032819 reaction equation
[CH3:1][C:2]1[N:12]=[CH:11][CH:10]=[CH:9][C:3]=1[C:4]([O:6][CH2:7][CH3:8])=[O:5].[Cl:13]C1C=C(C=CC=1)C(OO)=O.P(Cl)(Cl)(Cl)=O>C(Cl)Cl.ClCCCl>[Cl:13][CH2:1][C:2]1[N:12]=[CH:11][CH:10]=[CH:9][C:3]=1[C:4]([O:6][CH2:7][CH3:8])=[O:5]

Participants

6

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 70297m-Chloroperbenzoic acidHCID 74401Ethyl 2-methylnicotinate

Product 1

HCID 13170694Ethyl 2-(chloromethyl)pyridine-3-carboxylateYield 11%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 9 g of ethyl 2-methylnicotinate in 250 mL methylene chloride is stirred at room temperature and 32 g of 80% metachloroperoxybenzoic acid is added in one portion. The resulting solution is stirred for three days. The precipitated solid is filtered off, and the filtrate is washed with cold, dilute aqueous sodium hydroxide, dried, and concentrated in vacuo to afford the crude N-oxide. This material is digested in 75 mL of 1,2-dichloroethane; 15 mL of phosphorous oxychloride is added, and the solution is heated at reflux overnight. The solution is concentrated in vacuo, and the residue is taken up in methylene chloride and neutralized with aqueous sodium acetate. The organic phase is dried, concentrated in vacuo, and the residue is chromatographed on silica gel using hexane-ethyl acetate mixtures to afford 1.2 g of the title product as an oil having NMRδmCDCl3): 1.4 (+, 3H), 4.5 (q, 2H), 5.1 (2H), 7.4 (, 1H), 8.4 (dd, 1H), 8.8 (dd, 1H).

Workup

  1. filtrationThe precipitated solid is filtered off
  2. washthe filtrate is washed with cold, dilute aqueous sodium hydroxide
  3. customdried
  4. concentrationconcentrated in vacuo
  5. customto afford the crude N-oxide
  6. temperaturethe solution is heated
  7. temperatureat reflux overnight
  8. concentrationThe solution is concentrated in vacuo
  9. customThe organic phase is dried
  10. concentrationconcentrated in vacuo
  11. customthe residue is chromatographed on silica gel

Sources & evidence

ORD record
ord-b63ca32687a9412fb73e3df8398288a3
Source dataset
uspto-grants-1990_09
Patent number
US04959476

Reaction notes

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