2,4-Dichloropyridine → 3-Chloro-4-(2-chloropyridin-4-yloxy)-2-fluoroaniline

HRID 2279048Notes

Reaction equation

HRID 2279048 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([Cl:9])[C:3]=1[F:10].CC([O-])(C)C.[K+].[Cl:17][C:18]1[CH:23]=[C:22](Cl)[CH:21]=[CH:20][N:19]=1>CC(N(C)C)=O>[Cl:9][C:4]1[C:3]([F:10])=[C:2]([CH:7]=[CH:6][C:5]=1[O:8][C:22]1[CH:21]=[CH:20][N:19]=[C:18]([Cl:17])[CH:23]=1)[NH2:1]

Participants

5

Reactant 3

HCID 335152,4-DichloropyridineHCID 231052224-Amino-2-chloro-3-fluorophenolHCID 23665647Potassium tert-butoxide

Product 1

HCID 904256883-Chloro-4-(2-chloropyridin-4-yloxy)-2-fluoroanilineYield 59%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

A mixture of 4-amino-2-chloro-3-fluorophenol (11 g, 68.3 mmol) and potassium 2-methylpropan-2-olate (8.4 g, 75.2 mmol) in DMA (120 mL) was stirred at RT under N2 for 0.5 h, treated with 2,4-dichloropyridine (9.1 g, 62.1 mmol), and heated at 80° C. for 8 h. The mixture was concentrated to dryness, the residue treated with water, extracted with EtOAc (3×) and the combined organics were washed with brine, dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography to afford 3-chloro-4-(2-chloropyridin-4-yloxy)-2-fluoroaniline (10 g, 59%). 1H NMR (400 MHz, DMSO-d6): δ 8.26 (d, J=5.6 Hz, 1H), 6.98-6.96 (m, 2 H), 6.88 (dd, J=5.6 Hz, 2.0 Hz, 1 H), 6.80 (t, J=9.2 Hz, 1 H), 5.57 (s, 2H).

Workup

  1. temperatureheated at 80° C. for 8 h
  2. concentrationThe mixture was concentrated to dryness
  3. additionthe residue treated with water
  4. extractionextracted with EtOAc (3×)
  5. washthe combined organics were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated to dryness
  8. custompurified via silica gel chromatography

Sources & evidence

ORD record
ord-5b3221187163439285600a1a2af088f4
Source dataset
uspto-grants-2015_09
Patent number
US09133183B2

Reaction notes

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