1-Fluoro-3-nitrobenzene → 3-Chloro-5-(3-nitrophenoxy)pyridine

HRID 1696446Notes

Reaction equation

HRID 1696446 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([OH:8])[CH:5]=[N:6][CH:7]=1.[H-].[Na+].F[C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([N+:18]([O-:20])=[O:19])[CH:13]=1>CS(C)=O>[Cl:1][C:2]1[CH:7]=[N:6][CH:5]=[C:4]([O:8][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([N+:18]([O-:20])=[O:19])[CH:13]=2)[CH:3]=1

Participants

5

Reactant 3

HCID 98231-Fluoro-3-nitrobenzeneHCID 24758Sodium hydrideHCID 5823053-Hydroxy-5-chloropyridine

Product 1

HCID 229938583-Chloro-5-(3-nitrophenoxy)pyridineYield 23%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
120 °C

Procedure

A solution of 5-chloro-3-hydroxypyridine (0.45 g, 3.5 mmol) and NaH (0.15 g of 60% dispersion, 3.83 mmol) in DMSO (10 mL) was stirred at RT for 30 min and then treated with 1-fluoro-3-nitrobenzene (0.69 g, 4.9 mmol). The mixture was heated at 120° C. for 24 h, cooled to RT, quenched with satd. NH4Cl (50 mL), and extracted with EtOAc (3×25 mL). The combined organic extracts were washed with brine, dried (Na2SO4) and concentrated to yield a crude residue which was purified via column chromatography using to yield 3-chloro-5-(3-nitrophenoxy)pyridine (0.2 g, 23% yield) as a yellow solid. 1H NMR (400 MHz, CDCl3): □ 8.46 (d, J=−2.0 Hz, 1H), 8.35 (d, J=2.0 Hz, 1H), 8.09 (dd, J=8.4 Hz, 2.0 Hz, 1H), 7.89 (t, J=2.0 Hz, 1H), 7.60 (t, J=8.0 Hz, 1H), 7.41-7.39 (m, 2H); MS (ESI) m/z: 251.0 (M+H+).

Workup

  1. temperaturecooled to RT
  2. customquenched with satd
  3. extractionNH4Cl (50 mL), and extracted with EtOAc (3×25 mL)
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customto yield a crude residue which
  8. customwas purified via column chromatography

Sources & evidence

ORD record
ord-80d61789700d49dd817e65f1550769ad
Source dataset
uspto-grants-2012_04
Patent number
US08163756B2

Reaction notes

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