Sodium hydride → 5-Bromo-1((2-(trimethylsilyl)ethoxy)methyl)pyridin-2(1H)-one

HRID 595907Notes

Reaction equation

HRID 595907 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5](=[O:8])[NH:6][CH:7]=1.[H-].[Na+].Cl[CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17]>CN(C=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5](=[O:8])[N:6]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[CH:7]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 5995285-Bromo-2-hydroxypyridineHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl ether

Product 1

HCID 1233599985-Bromo-1((2-(trimethylsilyl)ethoxy)methyl)pyridin-2(1H)-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-bromopyridin-2(1H)-one (2.01 g, 11.55 mmol) in DMF (30 mL) at 0° C. was added sodium hydride (0.924 g, 23.10 mmol). The reaction mixture was stirred for 1 h at room temperature. To this, (2-(chloromethoxy)ethyl)trimethylsilane (2.89 g, 17.33 mmol) was added slowly. The reaction mixture was stirred overnight. LCMS—0.26 min, MH+ 304.1 (non-polar method). The reaction was quenched with sat. aq. NH4Cl, and then diluted with ethyl acetate. The reaction mixture was extracted with EtOAc. The combined organics were washed with water and brine, then dried over sodium sulfate, filtered off and concentrated in vacuo. The crude product was purified by flash chromatography column using 0-50% EtOAc/heptane. 5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)pyridin-2(1H)-one was obtained as a yellow viscous liquid. LCMS (m/z): 304/306 (MH+), 0.95 min.

Workup

  1. stirringThe reaction mixture was stirred overnight
  2. custom0.26 min, MH+ 304.1 (non-polar method)
  3. customThe reaction was quenched with sat. aq. NH4Cl
  4. additiondiluted with ethyl acetate
  5. extractionThe reaction mixture was extracted with EtOAc
  6. washThe combined organics were washed with water and brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered off
  9. concentrationconcentrated in vacuo
  10. customThe crude product was purified by flash chromatography column

Sources & evidence

ORD record
ord-0e0dc10f94b04d3e871d25f956398f50
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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