Potassium Carbonate → N-{4-chloro-2-fluoro-5-[(5-nitropyridin-2-yl)oxy]phenyl}-3-(1-cyano-1-methylethyl)benzamide

HRID 1800520Notes

Reaction equation

HRID 1800520 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][N:3]=1.[Cl:11][C:12]1[C:17]([OH:18])=[CH:16][C:15]([NH:19][C:20](=[O:32])[C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([C:30]#[N:31])([CH3:29])[CH3:28])[CH:22]=2)=[C:14]([F:33])[CH:13]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[Cl:11][C:12]1[C:17]([O:18][C:2]2[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][N:3]=2)=[CH:16][C:15]([NH:19][C:20](=[O:32])[C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([C:30]#[N:31])([CH3:29])[CH3:28])[CH:22]=2)=[C:14]([F:33])[CH:13]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 783082-Chloro-5-nitropyridineHCID 68419052N-(4-chloro-2-fluoro-5-hydroxyphenyl)-3-(1-cyano-1-methylethyl)benzamide

Product 1

HCID 68420111N-{4-chloro-2-fluoro-5-[(5-nitropyridin-2-yl)oxy]phenyl}-3-(1-cyano-1-methylethyl)benzamideYield 83.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 2-chloro-5-nitropyridine (952 mg, 6.01 mmol) and N-(4-chloro-2-fluoro-5-hydroxyphenyl)-3-(1-cyano-1-methylethyl)benzamide (2.00 g, 6.01 mmol) in N,N-dimethylformamide (20 mL) was added potassium carbonate (1.24 g, 9.01 mmol), and the mixture was stirred at 80° C. for 16 hr. The reaction mixture was cooled to room temperature, the insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. Water (100 mL) was added to the obtained residue, and the mixture was extracted with ethyl acetate (200 mL and 100 mL). The combined organic layer was washed with 5% aqueous sodium hydrogen carbonate solution (200 mL) and saturated brine (200 mL×2), and dried over anhydrous sodium sulfate. The insoluble material was filtered off, the filtrate was concentrated under reduced pressure, and the obtained residue was purified by basic silica gel column chromatography (ethyl acetate). The obtained solution was concentrated under reduced pressure to give the title compound (2.28 g, 83%) as a yellow oil.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationthe insoluble material was filtered off
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. additionWater (100 mL) was added to the obtained residue
  5. extractionthe mixture was extracted with ethyl acetate (200 mL and 100 mL)
  6. washThe combined organic layer was washed with 5% aqueous sodium hydrogen carbonate solution (200 mL) and saturated brine (200 mL×2)
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationThe insoluble material was filtered off
  9. concentrationthe filtrate was concentrated under reduced pressure
  10. customthe obtained residue was purified by basic silica gel column chromatography (ethyl acetate)
  11. concentrationThe obtained solution was concentrated under reduced pressure

Sources & evidence

ORD record
ord-565fd55036224293a63948939f4df1aa
Source dataset
uspto-grants-2013_01
Patent number
US08344135B2

Reaction notes

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