Acetic Anhydride → 2-Hydroxymethyl-4-propoxypyridine

HRID 4700Notes

Reaction equation

HRID 4700 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][CH2:10][CH3:11])[CH:5]=[CH:4][N+:3]=1[O-].C(OC(=O)C)(=[O:15])C.C(=O)([O-])[O-].[Na+].[Na+]>S(=O)(=O)(O)O>[OH:15][CH2:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][CH2:10][CH3:11])[CH:5]=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 10340Sodium CarbonateHCID 140971132-Methyl-4-propoxypyridine-1-oxide

Product 1

HCID 140971142-Hydroxymethyl-4-propoxypyridine

Reagents, catalysts & solvents 1

HCID 1118Sulfuric AcidCatalyst

Conditions

Temperature
100 °C

Procedure

A mixture of 2-methyl-4-propoxypyridine-1-oxide (8.6 g), acetic anhydride (8.6 ml) and concentrated sulfuric acid (two drops) was heated at 100° C. for five minutes, to which were added ice-water and an excess amount of sodium carbonate. The mixture was subjected to extraction with chloroform. The extract was dried with sodium sulfate, and the solvent was evaporated off. The residue was chromatographed on a column of silica-gel (200 g), which was eluted with carbon tetrachloride-acetone (5:3). The eluate was subjected to evaporation to remove the solvent. The residue (7.3 g) was dissolved in a solution of potassium hydroxide (2.8 g) in a mixture of water (3 ml) and methanol (60 ml). The resultant solution was stirred at room temperature for 15 minutes, to which were added ice-water and an excess amount of sodium carbonate. The mixture was subjected to extraction with ethyl acetate. The extract was dried with sodium sulfate, then the solvent was evaporated off. The residue was chromatographed on a column of silica-gel (150 g), which was eluted with 5% methanol-chloroform to yield 2-hydroxymethyl-4-propoxypyridine (4.4 g) as an oily substance.

Workup

  1. extractionThe mixture was subjected to extraction with chloroform
  2. dry with materialThe extract was dried with sodium sulfate
  3. customthe solvent was evaporated off
  4. customThe residue was chromatographed on a column of silica-gel (200 g), which
  5. washwas eluted with carbon tetrachloride-acetone (5:3)
  6. customThe eluate was subjected to evaporation
  7. customto remove the solvent
  8. dissolutionThe residue (7.3 g) was dissolved in a solution of potassium hydroxide (2.8 g) in a mixture of water (3 ml) and methanol (60 ml)
  9. additionwere added ice-water
  10. extractionThe mixture was subjected to extraction with ethyl acetate
  11. dry with materialThe extract was dried with sodium sulfate
  12. customthe solvent was evaporated off
  13. customThe residue was chromatographed on a column of silica-gel (150 g), which
  14. washwas eluted with 5% methanol-chloroform

Sources & evidence

ORD record
ord-167b86074bc5488b9fcafaa508255281
Source dataset
uspto-grants-1988_02
Patent number
US04727150

Reaction notes

Loading…