Sodium hydride → Pyridine, 6-(difluoromethoxy)-2-methyl-3-nitro-

HRID 510487Notes

Reaction equation

HRID 510487 reaction equation
[CH3:1][C:2]1[N:7]=[C:6]([OH:8])[CH:5]=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10].[H-].[Na+].[F:14][C:15]([F:23])(S(F)(=O)=O)C(O)=O>C(#N)C>[F:14][CH:15]([F:23])[O:8][C:6]1[N:7]=[C:2]([CH3:1])[C:3]([N+:9]([O-:11])=[O:10])=[CH:4][CH:5]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27375162,2-Difluoro-2-(fluorosulfonyl)acetic acidHCID 178433443HCID 178433443, compound

Product 1

HCID 89559033Pyridine, 6-(difluoromethoxy)-2-methyl-3-nitro-Yield 76.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 6-methyl-5-nitropyridin-2-ol (0.5 g, 3.2 mmol) in acetonitrile (10 mL) was added NaH (0.35 g, 8.64 mmol) and the reaction mixture was stirred for 15 minutes at room temperature. To the reaction mixture was added 2,2-difluoro-2-(fluoro-sulfonyl)acetic acid (1.1 mL, 5.5 mmol) dropwise. The reaction mixture was stirred for a further 15 minutes. The reaction mixture was then quenched by the addition of water, and diluted with EtOAc. The organic layer was washed with water and brine, dried over sodium sulphate and concentrated. The crude material obtained was purified by column chromatography (silica: 100-200 mesh, MeOH:DCM 2-4%) to afford the title compound (0.5 g, 75%) as a white solid. LCMS (ES−) 202.85 (M−H)−, RT 2.75 minutes (method 1).

Workup

  1. stirringThe reaction mixture was stirred for a further 15 minutes
  2. customThe reaction mixture was then quenched by the addition of water
  3. additiondiluted with EtOAc
  4. washThe organic layer was washed with water and brine
  5. dry with materialdried over sodium sulphate
  6. concentrationconcentrated
  7. customThe crude material obtained
  8. customwas purified by column chromatography (silica: 100-200 mesh, MeOH:DCM 2-4%)

Sources & evidence

ORD record
ord-929e922aef344084826f680bcf033da2
Source dataset
uspto-grants-2015_08
Patent number
US09096614B2

Reaction notes

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