Dimethylformamide → Methyl 6-(hydroxymethyl)picolinate

HRID 1871960Notes

Reaction equation

HRID 1871960 reaction equation
[N:1]1[C:6]([C:7]([OH:9])=O)=[CH:5][CH:4]=[CH:3][C:2]=1[C:10]([OH:12])=[O:11].[CH3:13]N(C)C=O>S(Cl)(Cl)=O>[OH:9][CH2:7][C:6]1[N:1]=[C:2]([C:10]([O:12][CH3:13])=[O:11])[CH:3]=[CH:4][CH:5]=1

Participants

4

Reactant 2

HCID 6228DimethylformamideHCID 103672,6-Pyridinedicarboxylic acid

Product 1

HCID 11513809Methyl 6-(hydroxymethyl)picolinate

Reagents, catalysts & solvents 1

HCID 24386Thionyl ChlorideSolvent

Procedure

A mixture of 2,6-pyridinedicarboxylic acid (10 g) in thionyl chloride (40 ml) with catalytic dimethylformamide was heated at reflux for 4 hours. The mixture was evaporated to dryness and azeotroped with toluene. Toluene (20 ml) was added to the residue followed by methanol (20 ml). The solvent was evaporated and the residue was partitioned between ethyl acetate and aqueous sodium bicarbonate. The organic phase was dried (MgSO4) and evaporated. The residue was dissolved in methanol and sodium borohydride (0.96 g) was added. The mixture was heated at reflux for 2 hours and evaporated. The residue was partitioned between chloroform and water. The organic phase was dried (MgSO4) and evaporated. Purification was by chromatography eluting with 5% methanol in chloroform. Yield 2.76 g.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 4 hours
  3. customThe mixture was evaporated to dryness
  4. customazeotroped with toluene
  5. additionToluene (20 ml) was added to the residue
  6. customThe solvent was evaporated
  7. customthe residue was partitioned between ethyl acetate and aqueous sodium bicarbonate
  8. dry with materialThe organic phase was dried (MgSO4)
  9. customevaporated
  10. dissolutionThe residue was dissolved in methanol
  11. additionsodium borohydride (0.96 g) was added
  12. temperatureThe mixture was heated
  13. temperatureat reflux for 2 hours
  14. customevaporated
  15. customThe residue was partitioned between chloroform and water
  16. dry with materialThe organic phase was dried (MgSO4)
  17. customevaporated
  18. customPurification
  19. washeluting with 5% methanol in chloroform

Sources & evidence

ORD record
ord-5b3d631811f541d4a8b9aaacfd334d25
Source dataset
uspto-grants-2000_08
Patent number
US06107297

Reaction notes

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