Ammonium Chloride → 1-(5-Bromo-2-methoxypyridin-3-yl)ethan-1-one

HRID 1776891Notes

Reaction equation

HRID 1776891 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][C:5]([O:14][CH3:15])=[C:6]([CH:13]=1)[C:7](N(OC)C)=[O:8].[CH3:16][Mg+].[Br-].[NH4+].[Cl-]>C1COCC1>[Br:1][C:2]1[CH:13]=[C:6]([C:7](=[O:8])[CH3:16])[C:5]([O:14][CH3:15])=[N:4][CH:3]=1

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 594686735-bromo-N,2-dimethoxy-N-methylnicotinamideHCID 178418689HCID 178418689, compound

Product 1

HCID 712951831-(5-Bromo-2-methoxypyridin-3-yl)ethan-1-oneYield 71.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
20 °C

Procedure

To a solution of 5-bromo-N,2-dimethoxy-N-methylnicotinamide (5.0 g, 18.18 mmol) in THF (50 mL), MeMgBr (10 mL, 30.0 mmol) was added dropwise at −78° C. The reaction mixture was stirred at 20° C. overnight. Then the reaction mixture was added to NH4Cl solution. The mixture was extracted with EtOAc. The combined organic phases were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified using column chromatography (eluted with petroleum ether:EtOAc=10:1) to provide 1-(5-bromo-2-methoxypyridin-3-yl)ethanone (3.0 g, yield: 71%). 1H-NMR (CDCl3, 400 MHz) δ 8.33 (d, J=2.4 Hz, 1H), 8.19 (d, J=2.4 Hz, 1H), 4.03 (s, 3H), 2.63 (s, 3H). MS (M+H)+: 230/232

Workup

  1. extractionThe mixture was extracted with EtOAc
  2. washThe combined organic phases were washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified
  7. washcolumn chromatography (eluted with petroleum ether:EtOAc=10:1)

Sources & evidence

ORD record
ord-8ed268f8bdb0431e8f8c138d82870ea9
Source dataset
uspto-grants-2016_02
Patent number
US09265773B2

Reaction notes

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