2-Methyl-5-hydroxypyridine → 6-[(4-Hydroxyoxan-4-yl)methyl]pyridin-3-ol

HRID 602451Notes

Reaction equation

HRID 602451 reaction equation
[CH3:1][C:2]1[N:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.C([Li])CCC.[O:14]1[CH2:19][CH2:18][C:17](=[O:20])[CH2:16][CH2:15]1>O1CCCC1>[OH:20][C:17]1([CH2:1][C:2]2[N:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=2)[CH2:18][CH2:19][O:14][CH2:15][CH2:16]1

Participants

5

Reactant 3

HCID 142752-Methyl-5-hydroxypyridineHCID 121599Tetrahydro-4H-pyran-4-oneHCID 178418339Butyllithium

Product 1

HCID 672702196-[(4-Hydroxyoxan-4-yl)methyl]pyridin-3-olYield 82%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred suspension of 6-methylpyridin-3-ol (5.01 g, 45.9 mmol) in tetrahydrofuran (200 mL) was added n-butyllithium solution (1.6 M in n-hexane, 63 mL, 101 mmol) dropwise at −20° C. After addition, the mixture was allowed to warm to room temperature and stirred at the same temperature for 1 h. Then the mixture was cooled to −78° C., and tetrahydro-4H-pyran-4-one (5.06 g, 50.5 mmol) was added dropwise. The mixture was allowed to warm to room temperature over 20 h. The mixture was quenched with acetic acid (11.6 mL) and concentrated under reduced pressure. The resulting residue was chromatographed on a column of silica gel eluting with acetone/n-hexane (1:1 to 2:1) to give 7.87 g (82%) of the title compound as a yellow oil.

Workup

  1. additionAfter addition
  2. temperatureThen the mixture was cooled to −78° C.
  3. temperatureto warm to room temperature over 20 h
  4. customThe mixture was quenched with acetic acid (11.6 mL)
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was chromatographed on a column of silica gel eluting with acetone/n-hexane (1:1 to 2:1)

Sources & evidence

ORD record
ord-24a2028f73ee4f9d8955b7a34c693417
Source dataset
uspto-grants-2011_03
Patent number
US07906532B2

Reaction notes

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