2,4-Dichloropyridine → 4-(2-Chloro-pyridin-4-yloxy)-2-fluoro-3-methyl-phenylamine

HRID 450425Notes

Reaction equation

HRID 450425 reaction equation
CC(C)([O-])C.[K+].[NH2:7][C:8]1[CH:13]=[CH:12][C:11]([OH:14])=[C:10]([CH3:15])[C:9]=1[F:16].[Cl:17][C:18]1[CH:23]=[C:22](Cl)[CH:21]=[CH:20][N:19]=1>CC(N(C)C)=O>[Cl:17][C:18]1[CH:23]=[C:22]([O:14][C:11]2[CH:12]=[CH:13][C:8]([NH2:7])=[C:9]([F:16])[C:10]=2[CH3:15])[CH:21]=[CH:20][N:19]=1

Participants

5

Reactant 3

HCID 335152,4-DichloropyridineHCID 23665647Potassium tert-butoxideHCID 552890104-Amino-3-fluoro-2-methylphenol

Product 1

HCID 866196704-(2-Chloro-pyridin-4-yloxy)-2-fluoro-3-methyl-phenylamineYield 42.2%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent2×

Procedure

Potassium tert-butoxide (3.5 g, 31 mmol) was added to a solution of 4-amino-3-fluoro-2-methyl-phenol (4.2 g, 30 mmol) in dimethylacetamide. The mixture was stirred at RT for 30 min. A solution of 2,4-dichloropyridine (4.38 g, 30 mmol) in dimethylacetamide was added and the mixture was heated at 100° C. overnight. The reaction mixture was concentrated in vacuo and the residue was dissolved in ethyl acetate (200 mL) and filtered through silica gel. The filter cake was washed with ethyl acetate, the combined filtrates were concentrated in vacuo and purified by silica gel chromatography to give 4-(2-chloro-pyridin-4-yloxy)-2-fluoro-3-methyl-phenylamine (3.2 g, 42% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.21 (d, J=6.4 Hz, 1H), 6.84 (d, J=2.0 Hz, 1H), 6.81 (dd, J=5.6, 2.4 Hz, 1H), 6.67-6.65 (m, 2H), 5.13 (s, 2H), 1.91 (s, 3H); MS (ESI): m/z 253.2 [M+H]+.

Workup

  1. temperaturethe mixture was heated at 100° C. overnight
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. dissolutionthe residue was dissolved in ethyl acetate (200 mL)
  4. filtrationfiltered through silica gel
  5. washThe filter cake was washed with ethyl acetate
  6. concentrationthe combined filtrates were concentrated in vacuo
  7. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-31ef9dcc243b48dda4d4c79dd70a8c9d
Source dataset
uspto-grants-2013_07
Patent number
US08486951B2

Reaction notes

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