2,2,2-Trifluoro-1-methoxyethanol → 6-methyl-2-(2,2,2-trifluoro-1-hydroxyethyl)pyridin-3-ol

HRID 1367817Notes

Reaction equation

HRID 1367817 reaction equation
[CH3:1][C:2]1[N:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.C[O:10][CH:11](O)[C:12]([F:15])([F:14])[F:13].C(=O)([O-])[O-].[K+].[K+]>>[CH3:1][C:2]1[N:7]=[C:6]([CH:11]([OH:10])[C:12]([F:15])([F:14])[F:13])[C:5]([OH:8])=[CH:4][CH:3]=1

Participants

4

Reactant 3

HCID 98922,2,2-Trifluoro-1-methoxyethanolHCID 11430Potassium CarbonateHCID 142752-Methyl-5-hydroxypyridine

Product 1

HCID 27830686-methyl-2-(2,2,2-trifluoro-1-hydroxyethyl)pyridin-3-olYield 66.1%

Conditions

Temperature
180 °C

Procedure

A mixture of commercially available 6-methylpyridin-3-ol (500 mg), trifluoroacetaldehyde methylhemiacetal (715 mg) and potassium carbonate (69 mg) was heated in a microwave reactor at 180° C. for 3 min. The reaction mixture was partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate. The combined organics were dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by silica gel chromatography using 1:1 hexane:ethyl acetate and recrystallized from ethyl acetate and hexane to give 627 mg of 6-methyl-2-(2,2,2-trifluoro-1-hydroxyethyl)pyridin-3-ol.

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate and water
  2. extractionThe aqueous layer was extracted with ethyl acetate
  3. dry with materialThe combined organics were dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by silica gel chromatography
  7. customethyl acetate and recrystallized from ethyl acetate and hexane

Sources & evidence

ORD record
ord-b18f12d2f1714541b2a499c437883678
Source dataset
uspto-grants-2011_02
Patent number
US07893093B2

Reaction notes

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