Sodium chlorodifluoroacetate → 2-(Difluoromethoxy)-5-nitropyridine

HRID 217277Notes

Reaction equation

HRID 217277 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][N:3]=1.Cl[C:12]([F:17])([F:16])C([O-])=O.[Na+]>C(#N)C>[F:16][CH:12]([F:17])[O:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][N:3]=1.[F:16][CH:12]([F:17])[N:3]1[CH:4]=[C:5]([N+:8]([O-:10])=[O:9])[CH:6]=[CH:7][C:2]1=[O:1]

Participants

5

Reactant 2

HCID 2734985Sodium chlorodifluoroacetateHCID 178526703HCID 178526703, compound

Product 2

HCID 160796311-difluoromethyl-5-nitro-1H-pyridin-2-oneYield 1.5%HCID 534037522-(Difluoromethoxy)-5-nitropyridineYield 15%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

2-Hydroxy-5-nitro-pyridine (5 g) was treated with sodium chlorodifluoro-acetate (11.5 g) in refluxing acetonitrile (186 ml) for 2 days. The solvent was evaporated, the residue poured into ethyl acetate, washed with brine, dried over sodium sulfate and then concentrated in vacuo. Chromatography on silica gel (eluent: hexane/ethyl acetate 1:1) afforded 2-difluoromethoxy-5-nitro-pyridine (1 g, 15%) and 1-difluoromethyl-5-nitro-1H-pyridin-2-one (90 mg, 1.5%). 2-Difluoromethoxy-5-nitro-pyridine: MS (ES+) 191 (MH+); 1H NMR (400 MHz, CDCl3) 7.05 (d, 1H), 7.51 (t, 1H), 8.53 (dd, 1H), 9.09 (d, 1H). 1-Difluoromethyl-5-nitro-1H-pyridin-2-one: MS (ES+) 191 (MH+); 6.65 (d, 1H), 7.63 (t, 1H), 8.14 (dd, 1H), 8.73 (d, 1H).

Workup

  1. customThe solvent was evaporated
  2. additionthe residue poured into ethyl acetate
  3. washwashed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-615bcd8775b74cb189da5b1ec0defd94
Source dataset
uspto-grants-2012_06
Patent number
US08193362B2

Reaction notes

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