Phenol, 4-amino-2-fluoro- → 4-(4-Amino-2-fluorophenoxy)-3-chloropicolinamide

HRID 520665Notes

Reaction equation

HRID 520665 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([F:9])[CH:3]=1.CC([O-])(C)C.[K+].[Cl:16][C:17]1[C:18]([C:24]([NH2:26])=[O:25])=[N:19][CH:20]=[CH:21][C:22]=1Cl>CN(C=O)C>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:22]2[CH:21]=[CH:20][N:19]=[C:18]([C:24]([NH2:26])=[O:25])[C:17]=2[Cl:16])=[C:4]([F:9])[CH:3]=1

Participants

5

Reactant 3

HCID 2735918Phenol, 4-amino-2-fluoro-HCID 231651433,4-Dichloropyridine-2-carboxamideHCID 23665647Potassium tert-butoxide

Product 1

HCID 252319754-(4-Amino-2-fluorophenoxy)-3-chloropicolinamideYield 54.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-amino-2-fluorophenol (254 mg, 2.0 mmol) in DMF (5 mL) was added t-BuOK (359 mg, 3.2 mmol). The mixture was stirred at rt for 30 minutes. 3,4-dichloropicolinamide (420 mg, 2.2 mmol) was then added, and the mixture was microwaved at 120° C. for 2 hours. The mixture was cooled to rt, quenched with 25 mL of water. The resulted solution was extracted with EtOAc (30 mL×3) and the combined organic phases were washed with brine (30 mL×3), dried over Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (EtOAc/PE (v/v)=2/1) to give the title compound as a pale yellow solid (306 mg, 54.4%).

Workup

  1. customthe mixture was microwaved at 120° C. for 2 hours
  2. temperatureThe mixture was cooled to rt
  3. customquenched with 25 mL of water
  4. extractionThe resulted solution was extracted with EtOAc (30 mL×3)
  5. washthe combined organic phases were washed with brine (30 mL×3)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by a silica gel column chromatography (EtOAc/PE (v/v)=2/1)

Sources & evidence

ORD record
ord-d415ea83376e43ffa6ec1fe2bf97f52f
Source dataset
uspto-grants-2016_05
Patent number
US09326975B2

Reaction notes

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