Sodium Iodide → 2-fluoro-N-(2-oxo-1H-pyridin-4-yl)-4,6-bis(trifluoromethyl)benzamide

HRID 2170428Notes

Reaction equation

HRID 2170428 reaction equation
[I-].[Na+].C[Si](Cl)(C)C.[F:8][C:9]1[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[C:22]([C:30]([F:33])([F:32])[F:31])[C:10]=1[C:11]([NH:13][C:14]1[CH:19]=[CH:18][N:17]=[C:16]([O:20]C)[CH:15]=1)=[O:12]>C(#N)C.O>[F:8][C:9]1[CH:25]=[C:24]([C:26]([F:28])([F:29])[F:27])[CH:23]=[C:22]([C:30]([F:33])([F:31])[F:32])[C:10]=1[C:11]([NH:13][C:14]1[CH:19]=[CH:18][NH:17][C:16](=[O:20])[CH:15]=1)=[O:12]

Participants

6

Reactant 3

HCID 5238Sodium IodideHCID 6397ChlorotrimethylsilaneHCID 867284822-fluoro-N-(2-methoxy-4-pyridyl)-4,6-bis(trifluoromethyl)benzamide

Product 1

HCID 867284832-fluoro-N-(2-oxo-1H-pyridin-4-yl)-4,6-bis(trifluoromethyl)benzamideYield 83%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent2×

Conditions

Temperature
25 °C

Procedure

To a mixture of sodium iodide (2.54 g, 16.95 mmol) in acetonitrile (75 mL) under nitrogen was added TMSCl (2.15 mL, 16.95 mmol) and the mixture was stirred at 25° C. for 30 min. Thereafter, anhydrous acetonitrile (130.0 ml) was added to this solution followed by 2-fluoro-N-(2-methoxy-4-pyridyl)-4,6-bis(trifluoromethyl)benzamide (1.2 g, 3.14 mmol). The resulting reaction mixture was heated with stirring at 80° C. for 5 h and at 60° C. for 12 hours. The reaction was cooled, diluted with water, and extracted with ethyl acetate. The organic layer was dried over Na2SO4, filtered and concentrated to a dark yellow-orange solid. The solid was triturated with ethyl acetate/hexanes several times to remove dark red color, then with dichloromethane to remove yellow color, then finally with hexanes. The resulting solid was dried under vacuum to provide 2-fluoro-N-(2-oxo-1H-pyridin-4-yl)-4,6-bis(trifluoromethyl)benzamide (960 mg, 83%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ 11.41 (s, 1H), 11.03 (s, 1H), 8.41 (d, J=8.4 Hz, 1H), 8.16 (d, J=1.7 Hz, 1H), 7.37 (d, J=7.1 Hz, 1H), 6.71 (d, J=2.0 Hz, 1H), 6.31 (dd, J=7.2, 2.1 Hz, 1H) ppm. ESI-MS m/z calc. 368.04. found 369.1 (M+1)+; Retention time: 1.28 minutes (3 minutes run).

Workup

  1. customThe resulting reaction mixture
  2. temperaturewas heated
  3. stirringwith stirring at 80° C. for 5 h and at 60° C. for 12 hours
  4. temperatureThe reaction was cooled
  5. extractionextracted with ethyl acetate
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated to a dark yellow-orange solid
  9. customThe solid was triturated with ethyl acetate/hexanes several times
  10. customto remove dark red color
  11. customwith dichloromethane to remove yellow color
  12. customThe resulting solid was dried under vacuum

Sources & evidence

ORD record
ord-7e624bacdd05485a8660084761936975
Source dataset
uspto-grants-2015_06
Patent number
US09051270B2

Reaction notes

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