2,6-Dichloro-4-(trifluoromethyl)nicotinamide → 2,6-Dichloro-4-(trifluoromethyl)nicotinic acid

HRID 2214983Notes

Reaction equation

HRID 2214983 reaction equation
N([O-])=[O:2].[Na+].[Cl:5][C:6]1[N:14]=[C:13]([Cl:15])[CH:12]=[C:11]([C:16]([F:19])([F:18])[F:17])[C:7]=1[C:8](N)=[O:9]>O.OS(O)(=O)=O>[Cl:5][C:6]1[N:14]=[C:13]([Cl:15])[CH:12]=[C:11]([C:16]([F:19])([F:18])[F:17])[C:7]=1[C:8]([OH:2])=[O:9]

Participants

5

Reactant 2

HCID 27368742,6-Dichloro-4-(trifluoromethyl)nicotinamideHCID 23668193Sodium Nitrite

Product 1

HCID 219481962,6-Dichloro-4-(trifluoromethyl)nicotinic acidYield 95%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 1118Sulfuric AcidSolvent

Procedure

A solution of NaNO2 (9.59 g, 139 mmol) in water (95 mL) was added slowly to a solution of commercially available (Oakwood) 2,6-dichloro-4-(trifluoromethyl)nicotinamide (20.0 g, 77 mmol) in conc. H2SO4 resulting in evolution of heat and brown gas. The mixture was stirred at room temperature for 15 min, and then heated to 60° C. for 18 h. The solution was cooled to 0° C. and then water (15 mL) was added. The resulting mixture was extracted with Et2O (3×) and the combined organic extracts were dried over MgSO4 and concentrated in vacuo. The residue was triturated with hexanes and vacuum-filtered to afford 2,6-dichloro-4-(trifluoromethyl)nicotinic acid (19 g, 95%) as an off-white solid: Rf=0.30 (9:1 CH2Cl2:MeOH), 1H-NMR (d6-DMSO, 300 MHz) δ 8.18 (s, 1H).

Workup

  1. temperatureof heat
  2. temperatureheated to 60° C. for 18 h
  3. temperatureThe solution was cooled to 0° C.
  4. extractionThe resulting mixture was extracted with Et2O (3×)
  5. dry with materialthe combined organic extracts were dried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was triturated with hexanes
  8. filtrationvacuum-filtered

Sources & evidence

ORD record
ord-d1ef063c02d9479aac1ea9e9cc865357
Source dataset
uspto-grants-2006_09
Patent number
US07109196B2

Reaction notes

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