Water → 5-Chloro-4-(2-chloropyridin-4-yloxy)-2-fluorobenzenamine

HRID 1050849Notes

Reaction equation

HRID 1050849 reaction equation
[NH2:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([OH:9])=[C:4]([Cl:10])[CH:3]=1.[Cl:11][C:12]1[CH:17]=[C:16](Cl)[CH:15]=[CH:14][N:13]=1.C([O-])([O-])=O.[K+].[K+].O>CS(C)=O>[Cl:10][C:4]1[C:5]([O:9][C:16]2[CH:15]=[CH:14][N:13]=[C:12]([Cl:11])[CH:17]=2)=[CH:6][C:7]([F:8])=[C:2]([NH2:1])[CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 335152,4-DichloropyridineHCID 231052154-Amino-2-chloro-5-fluorophenol

Product 1

HCID 866416885-Chloro-4-(2-chloropyridin-4-yloxy)-2-fluorobenzenamineYield 32%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A solution of 4-amino-2-chloro-5-fluorophenol (6.0 g, 37 mmol), 2,4-dichloro-pyridine (5.3 g, 37 mmol) and K2CO3 (5.2 g, 37 mmol) in DMSO (100 mL) was heated at 80° C. under nitrogen overnight. The mixture was cooled to RT, poured into water (300 mL), and extracted with EtOAc (3×200 mL). The combined organics were washed with brine (3×100 mL), dried over Na2SO4, and concentrated in vacuo. The residue was purified by silica gel chromatography (EtOAc/petroleum ether) to give 5-chloro-4-(2-chloro-pyridin-4-yloxy)-2-fluoro-phenylamine as a white solid (3.0 g, 32% yield). 1H NMR (300 MHz, DMSO-d6): δ 8.33 (d, J=5.7 Hz, 1 H), 7.34-7.31 (m, 1 H), 7.01-6.82 (m, 3 H), 5.63 (br s, 2 H).

Workup

  1. extractionextracted with EtOAc (3×200 mL)
  2. washThe combined organics were washed with brine (3×100 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by silica gel chromatography (EtOAc/petroleum ether)

Sources & evidence

ORD record
ord-de3da4ce544a4ef8ae843b21335f8a72
Source dataset
uspto-grants-2016_07
Patent number
US09387202B2

Reaction notes

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