Water → 3-(2-Chloropyridin-4-yloxy)-4-fluorobenzoic acid methyl ester

HRID 521771Notes

Reaction equation

HRID 521771 reaction equation
[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([F:10])=[C:6]([OH:11])[CH:5]=1.[H-].[Na+].[Cl:15][C:16]1[CH:21]=[C:20]([N+]([O-])=O)[CH:19]=[CH:18][N:17]=1.O>CN(C)C=O>[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([F:10])=[C:6]([O:11][C:20]2[CH:19]=[CH:18][N:17]=[C:16]([Cl:15])[CH:21]=2)[CH:5]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 7351522-Chloro-4-nitropyridineHCID 120168924-Fluoro-3-hydroxy-benzoic acid methyl ester

Product 1

HCID 581679163-(2-Chloropyridin-4-yloxy)-4-fluorobenzoic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-Fluoro-3-hydroxybenzoic acid methyl ester (1.70 g, 10.0 mmol) was dissolved in dimethylformamide (9 mL) under nitrogen at room temperature. Sodium hydride (60% oil dispersion, 0.48 g, 12 mmol) was added in portions over 30 min. The reaction was stirred for 90 minutes and then cooled in an ice bath. 2-Chloro-4-nitropyridine (1.58 g, 10.0 mmol) was added in small portions over 50 min. The reaction was stirred at room temperature for 17.5 h. Water (200 ml) was added and the mixture stirred until a brown lump formed. The water was decanted and the residue dissolved in EtOAc (150 mL). The solution was washed with brine, dried (MgSO4), filtered and evaporated to give 3-(2-Chloropyridin-4-yloxy)-4-fluorobenzoic acid methyl ester. Yield: 3.10 g.

Workup

  1. temperaturecooled in an ice bath
  2. stirringThe reaction was stirred at room temperature for 17.5 h
  3. stirringthe mixture stirred until a brown lump
  4. customformed
  5. customThe water was decanted
  6. dissolutionthe residue dissolved in EtOAc (150 mL)
  7. washThe solution was washed with brine
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. customevaporated

Sources & evidence

ORD record
ord-20d5ae42732c45f1a068e4adb1648df6
Source dataset
uspto-grants-2016_05
Patent number
US09328103B2

Reaction notes

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