Reaction #7873

Reaction equation

AcOH

N-(pyridin-3-yl)-2,2-dimethylpropanamide

n-Butyllithium

trimethyl borate

H2O2

→

N-(4-hydroxypyridin-3-yl)-2,2-dimethylpropanamide

Solvents

THF

H2O

THF

Conditions

Workup

1. 1
   workup.ADDITIONAfter addition
2. 2
   TemperatureThe reaction was then cooled back to −78° C.
3. 3
   workup.ADDITIONAfter addition
4. 4
   Temperaturethe reaction mixture was warmed to 0° C.
5. 5
   workup.STIRRINGstirred an additional 2 h
6. 6
   TemperatureThe reaction mixture was warmed to rt
7. 7
   workup.STIRRINGstirred overnight
8. 8
   Concentrationconcentrated in vacuo
9. 9
   ExtractionThe residue was extracted three times with 10% iPrOH/CHCl3
10. 10
    workup.ADDITIONthe combined extracts treated with activated charcoal
11. 11
    Filtrationthe slurry filtered through Celite
12. 12
    WashThe organic layer was washed three times with H2O
13. 13
    Dryingonce with brine, dried over MgSO4
14. 14
    Filtrationfiltered
15. 15
    Concentrationconcentrated in vacuo
16. 16
    OtherThe residue was purified by column chromatography (3–10% MeOH/CHCl3)

Procedure

To a stirred solution of N-(pyridin-3-yl)-2,2-dimethylpropanamide (8.90 g, 50.0 mmol) in THF (200 mL) at −78° C. was added n-Butyllithium (50 mL, 125 mmol) dropwise over 30 min. After addition, the reaction mixture was warmed to 0° C. and stirred an additional 3 h. The reaction was then cooled back to −78° C. and trimethyl borate (14.2 mL, 125 mmol) in THF was added dropwise over 15 min. After addition, the reaction mixture was warmed to 0° C. and stirred an additional 2 h. Glacial AcOH (10.8 mL, 188 mmol) was added to the reaction, followed by dropwise addition of 30% H2O2 (14.3 mL, 138 mmol). The reaction mixture was warmed to rt and stirred overnight. The mixture was diluted with H2O and concentrated in vacuo. The residue was extracted three times with 10% iPrOH/CHCl3, the combined extracts treated with activated charcoal, and the slurry filtered through Celite. The organic layer was washed three times with H2O, once with brine, dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography (3–10% MeOH/CHCl3) to give N-(4-hydroxypyridin-3-yl)-2,2-dimethylpropanamide as a light yellow solid. 1H NMR (DMSO-d6, 300 MHz) δ 11.58 (br s, 1H), 8.76 (br s, 1H), 8.67 (s, 1H), 7.68 (d, 1H), 6.26 (d, 1H), 1.22 (s, 9H).

Source