1,4-Cyclohexadiene → 3-Methoxy-4-ethyl-6-(1-hydroxyethyl)-pyridine

HRID 1637770Notes

Reaction equation

HRID 1637770 reaction equation
Cl[C:2]1[C:7]([O:8][CH3:9])=[C:6]([CH:10]=[CH2:11])[CH:5]=[C:4]([CH:12]([OH:14])[CH3:13])[N:3]=1.C1CC=CCC=1>C(O)C.[Pd]>[CH3:9][O:8][C:7]1[CH:2]=[N:3][C:4]([CH:12]([OH:14])[CH3:13])=[CH:5][C:6]=1[CH2:10][CH3:11]

Participants

5

Reactant 2

HCID 123431,4-CyclohexadieneHCID 18799939HCID 18799939, compound

Product 1

HCID 187998333-Methoxy-4-ethyl-6-(1-hydroxyethyl)-pyridineYield 63%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

A solution of 2-chloro-3-methoxy-4-vinyl-6-(1-hydroxyethyl)-pyridine (485 mg, 2.27 mmol) in 10 mL of ethanol is treated with 485 mg of 20% palladium on carbon and 1,4-cyclohexadiene (2.0 mL, 21 mmol) and the reaction is refluxed for 4 h. The catalyst is removed by filtration through celite and the filter pad washed well with methanol. The filtrate is concentrated in vacuo and the residue is partitioned between 25 mL of saturated sodium bicarbonate and 4×25 mL of ethyl acetate. The combined organics are dried over potassium carbonate and concentrated in vacuo. The crude material is chromatographed over 20 g of silica gel (230-400 mesh), eluting with 100 mL of 50% ethyl acetate/hexanes followed by 80% ethyl acetate/hexanes to afford 256 mg (63%) of 3-methoxy-4-ethyl-6-(1-hydroxyethyl)-pyridine.

Workup

  1. temperaturethe reaction is refluxed for 4 h
  2. customThe catalyst is removed by filtration through celite
  3. washthe filter pad washed well with methanol
  4. concentrationThe filtrate is concentrated in vacuo
  5. customthe residue is partitioned between 25 mL of saturated sodium bicarbonate and 4×25 mL of ethyl acetate
  6. dry with materialThe combined organics are dried over potassium carbonate
  7. concentrationconcentrated in vacuo
  8. customThe crude material is chromatographed over 20 g of silica gel (230-400 mesh)
  9. washeluting with 100 mL of 50% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-cc6bc0f577314c5fbf018a5cc4072659
Source dataset
uspto-grants-2000_03
Patent number
US06043248

Reaction notes

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