Sodium Iodide → N-(6-Iodo-4-o-tolylpyridin-3-yl)-N-methyl-3,5-bis(trifluoromethyl)benzamide

HRID 877978Notes

Reaction equation

HRID 877978 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([N:8]([CH3:25])[C:9](=[O:24])[C:10]2[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[C:12]([C:20]([F:23])([F:22])[F:21])[CH:11]=2)=[C:4]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[CH3:32])[CH:3]=1.[I-:33].[Na+].I>CC(C)=O>[I:33][C:2]1[N:7]=[CH:6][C:5]([N:8]([CH3:25])[C:9](=[O:24])[C:10]2[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[C:12]([C:20]([F:23])([F:22])[F:21])[CH:11]=2)=[C:4]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[CH3:32])[CH:3]=1

Participants

5

Reactant 3

HCID 5238Sodium IodideHCID 24841Hydrogen iodideHCID 60197100N-(6-Chloro-4-o-tolyl-pyridin-3-yl)-N-methyl-3,5-bis-trifluoromethyl-benzamide

Product 1

HCID 86670689N-(6-Iodo-4-o-tolylpyridin-3-yl)-N-methyl-3,5-bis(trifluoromethyl)benzamide

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To N-(6-chloro-4-o-tolylpyridin-3-yl)-N-methyl-3,5-bis(trifluoromethyl)benzamide (460 mg, 0.97 mmol, example 12) in acetone (3 mL) was added sodium iodide (1.17 g, 7.8 mmol) and hydriodic acid (170 μL, 1.07 mmol). The reaction mixture was heated to reflux for 4 hours. Acetone was evaporated and acetonitrile (3 mL) was added and the reaction mixture heated again to reflux. After 16 hours, the reaction mixture was carefully neutralized with saturated aqueous NaHCO3 solution and extracted three times with EtOAc. The combined organic layers were washed with brine and dried over MgSO4. Filtration and removal of volatiles under reduced pressure afforded a brown solid. The desired compound was isolated by flash chromatography on silica gel (50% EtOAc in n-hexane) as an amber oil (324 mg, 59%).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 4 hours
  3. customAcetone was evaporated
  4. additionacetonitrile (3 mL) was added
  5. temperaturethe reaction mixture heated again
  6. temperatureto reflux
  7. extractionextracted three times with EtOAc
  8. washThe combined organic layers were washed with brine
  9. dry with materialdried over MgSO4
  10. filtrationFiltration and removal of volatiles under reduced pressure
  11. customafforded a brown solid

Sources & evidence

ORD record
ord-9a025470793541da9e55bfa18a26e1ec
Source dataset
uspto-grants-2015_03
Patent number
US08987307B2

Reaction notes

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