2,4-Dichloropyridine → 4-(2-Chloro-pyridin-4-yloxy)-2,3-difluorophenylamine

HRID 450416Notes

Reaction equation

HRID 450416 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([F:9])[C:3]=1[F:10].CC(C)([O-])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:17][C:18]1[CH:23]=[C:22]([O:8][C:5]2[CH:6]=[CH:7][C:2]([NH2:1])=[C:3]([F:10])[C:4]=2[F:9])[CH:21]=[CH:20][N:19]=1

Participants

5

Reactant 3

HCID 335152,4-DichloropyridineHCID 27787664-Amino-2,3-difluorophenolHCID 23665647Potassium tert-butoxide

Product 1

HCID 866238534-(2-Chloro-pyridin-4-yloxy)-2,3-difluorophenylamineYield 66%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

4-amino-2,3-difluorophenol (6 g, 41.4 mmol) and potassium tert-butoxide (4.9 g, 43.5 mmol) were suspended in DMAc (200 mL) and stirred at RT for 30 min under Ar atmosphere. 2,4-Dichloropyridine (6.1 g, 41.4 mmol) was added, and the resulting mixture was heated to 70° C. for 8 h. The reaction mixture was filtered, concentrated in vacuo and purified by silica gel chromatography to afford 4-(2-chloro-pyridin-4-yloxy)-2,3-difluoro-phenylamine (7 g, 66% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.27 (d, =6.0 Hz, 1H), 7.05 (s, 1H), 6.95 (m, 1H), 6.92 (m, 1H), 6.62 (m, 1H), 5.60 (s, 2H); MS (ESI) m/z: 257.1 [M+H]+.

Workup

  1. temperaturethe resulting mixture was heated to 70° C. for 8 h
  2. filtrationThe reaction mixture was filtered
  3. concentrationconcentrated in vacuo
  4. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-4d7af5729a4544c9971a354ee7949c61
Source dataset
uspto-grants-2013_07
Patent number
US08486951B2

Reaction notes

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