Water → 4-(2-Chloropyridin-4-yloxy)-3,5-difluoroaniline

HRID 450436Notes

Reaction equation

HRID 450436 reaction equation
CC(C)([O-])C.[K+].[NH2:7][C:8]1[CH:13]=[C:12]([F:14])[C:11]([OH:15])=[C:10]([F:16])[CH:9]=1.[Cl:17][C:18]1[CH:23]=[C:22](Cl)[CH:21]=[CH:20][N:19]=1.O>CN(C)C(=O)C>[Cl:17][C:18]1[CH:23]=[C:22]([O:15][C:11]2[C:12]([F:14])=[CH:13][C:8]([NH2:7])=[CH:9][C:10]=2[F:16])[CH:21]=[CH:20][N:19]=1

Participants

6

Reactant 4

HCID 962WaterHCID 335152,4-DichloropyridineHCID 27787644-Amino-2,6-difluorophenolHCID 23665647Potassium tert-butoxide

Product 1

HCID 866416864-(2-Chloropyridin-4-yloxy)-3,5-difluoroanilineYield 59%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent2×

Procedure

Potassium tert-butoxide (2.4 g, 22 mmol) was added to a solution of 4-amino-2,6-difluorophenol (2.9 g, 20 mmol) in N,N-dimethyl-acetamide (50 mL) and the mixture was stirred at RT under nitrogen for 0.5 h. A solution of 2,4-dichloro-pyridine (2.9 g, 20 mmol) in N,N-dimethyl-acetamide was added, and the reaction was heated to 100° C. under nitrogen for 10 h. After cooling to RT, the reaction was poured into water (100 mL) and the aqueous solution was extracted with ethyl acetate (3×70 mL). The combined organics were washed with brine, dried (Na2SO4), concentrated in vacuo and purified by silica gel chromatography to give 4-(2-chloropyridin-4-yloxy)-3,5-difluoroaniline (3.0 g, 59% yield). 1H NMR (300 MHz, DMSO-d6): δ 8.31 (d, J=5.7 Hz, 1H), 7.10 (d, J=2.1 Hz, 1H), 7.01 (dd, J=5.7 Hz, 2.1 Hz, 1H), 6.38 (d, J=10.8 Hz, 2H), 5.86 (s, 2H).

Workup

  1. temperaturethe reaction was heated to 100° C. under nitrogen for 10 h
  2. temperatureAfter cooling to RT
  3. extractionthe aqueous solution was extracted with ethyl acetate (3×70 mL)
  4. washThe combined organics were washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-28eb33819ca940bab6e908bdc37db5b1
Source dataset
uspto-grants-2013_07
Patent number
US08486951B2

Reaction notes

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