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

HRID 2279024Notes

Reaction equation

HRID 2279024 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 DMA, and stirred at RT for 0.5 h. A solution of 2,4-dichloropyridine (4.38 g, 30 mmol) in DMA was added and the mixture was heated at 100° C. overnight. The reaction mixture was concentrated in vacuo and the residue was dissolved in EtOAc (200 mL) and filtered through silica gel. The filter cake was washed with EtOAc, and 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, 1 H), 6.84 (d, J=2.0 Hz, 1H), 6.81 (dd, J=5.6, 2.4 Hz, 1 H), 6.67-6.65 (m, 2 H), 5.13 (s, 2 H), 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 EtOAc (200 mL)
  4. filtrationfiltered through silica gel
  5. washThe filter cake was washed with EtOAc
  6. concentrationthe combined filtrates were concentrated in vacuo
  7. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-68d57934e64e427e9bfcb9ec7f49bb2e
Source dataset
uspto-grants-2015_09
Patent number
US09133183B2

Reaction notes

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