Ammonium Persulfate → (4-(tert-Butyl)pyridin-2-yl)methanol

HRID 1637729Notes

Reaction equation

HRID 1637729 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][N+:8]([O-])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].F[B-](F)(F)F.[CH3:17][O+:18](C)C.S(OOS([O-])(=O)=O)([O-])(=O)=O.[NH4+].[NH4+]>ClCCl.O>[C:1]([C:5]1[CH:10]=[CH:9][N:8]=[C:7]([CH2:17][OH:18])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 62648Ammonium Persulfate2×HCID 1410394-(tert-Butyl)pyridine 1-OxideHCID 2735153Oxonium, trimethyl-, tetrafluoroborate(1-) (1:1)

Product 1

HCID 18799645(4-(tert-Butyl)pyridin-2-yl)methanolYield 73%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent

Procedure

4-t-Butyl-pyridine N-oxide (11.0 g, 72.9 mmole) is dissolved in 200 ml dichloromethane in a 500 ml one neck round bottom flask under nitrogen. The solution is treated with trimethyloxonium tetrafluoroborate (10.8 g, 72.9 mmole), is stirred 1h at room temperature, and the volatiles are removed in vacuo. The solid residue is dissolved in 200 ml methanol in a 500 ml one neck round bottom flask. The solution is heated to reflux, is treated with ammonium persulfate (3.3 g, 14.5 mmole) in 15 ml water, and the reaction mixture is vigorously refluxed for 30 min. The reaction is treated with a second lot of ammonium persulfate (1.65 g, 7.2 mmole) in 7 ml water and is refluxed for an additional 1 h. The reaction is cooled and the bulk of the methanol is removed in vacuo. The residue is diluted with 300 ml conc ammonium hydroxide and the mixture is extracted with 4×100 ml dichloromethane. The combined organics are dried over potassium carbonate and are concentrated in vacuo to a yellow oil. The crude material is chromatographed over 400 g silica gel (230-400 mesh), eluting with 40% acetone/hexane, while collecting 50 ml fractions. Fractions 26-52 are combined and concentrated to afford 8.79 g (73%) of 4-t-Butyl-2-hydroxymethyl-pyridine as a yellow oil.

Workup

  1. customthe volatiles are removed in vacuo
  2. dissolutionThe solid residue is dissolved in 200 ml methanol in a 500 ml one neck round bottom flask
  3. temperatureThe solution is heated
  4. temperatureto reflux
  5. temperaturethe reaction mixture is vigorously refluxed for 30 min
  6. temperatureis refluxed for an additional 1 h
  7. temperatureThe reaction is cooled
  8. customthe bulk of the methanol is removed in vacuo
  9. additionThe residue is diluted with 300 ml conc ammonium hydroxide
  10. extractionthe mixture is extracted with 4×100 ml dichloromethane
  11. dry with materialThe combined organics are dried over potassium carbonate
  12. concentrationare concentrated in vacuo to a yellow oil
  13. customThe crude material is chromatographed over 400 g silica gel (230-400 mesh)
  14. washeluting with 40% acetone/hexane
  15. customwhile collecting 50 ml fractions
  16. concentrationconcentrated

Sources & evidence

ORD record
ord-11a305d1ab044c10bb689311f2b04a4c
Source dataset
uspto-grants-2000_03
Patent number
US06043248

Reaction notes

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