Iodine → Methyl 4-amino-5-fluoro-6-(3-fluoro-4-(trifluoromethyl)phenyl)-3-iodopicolinate

HRID 407228Notes

Reaction equation

HRID 407228 reaction equation
[NH2:1][C:2]1[C:7]([F:8])=[C:6]([C:9]2[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[C:11]([F:19])[CH:10]=2)[N:5]=[C:4]([C:20]([O:22][CH3:23])=[O:21])[CH:3]=1.[I:24](O)(=O)(=O)=O.II>CO>[NH2:1][C:2]1[C:7]([F:8])=[C:6]([C:9]2[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[C:11]([F:19])[CH:10]=2)[N:5]=[C:4]([C:20]([O:22][CH3:23])=[O:21])[C:3]=1[I:24]

Participants

5

Reactant 3

HCID 807IodineHCID 65185Metaperiodic acidHCID 71150567Methyl 4-amino-5-fluoro-6-(3-fluoro-4-(trifluoromethyl)phenyl)picolinate

Product 1

HCID 71150644Methyl 4-amino-5-fluoro-6-(3-fluoro-4-(trifluoromethyl)phenyl)-3-iodopicolinateYield 255.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Methyl 4-amino-5-fluoro-6-(3-fluoro-4-(trifluoromethyl)phenyl)picolinate (500 mg, 1.51 mmol) was dissolved in CH3OH (0.6 mL) in a round bottom flask. Periodic acid (123 mg, 0.542 mmol) and iodine (306 mg, 1.204 mmol) were added, and the reaction mixture was heated at reflux with a drying tube for 12 h. The reaction mixture was cooled to room temperature and concentrated in vacuo. The crude product was dissolved in Et2O and washed with 10% sodium thiosulfate (Na2S2O3; 2×5 mL). The organic extracts were combined, dried over anhydrous Na2SO4, filtered, and concentrated providing methyl 4-amino-5-fluoro-6-(3-fluoro-4-(trifluoromethyl)phenyl)-3-iodopicolinate (635 mg, 92%): 1H NMR (400 MHz, DMSO-d6) δ 7.93 (dd, J=14.8, 6.8 Hz, 1H), 7.90-7.82 (m, 2H), 6.89 (s, 2H), 3.88 (s, 3H); 19F NMR (376 MHz, DMSO-d6) δ −60.02 (t, J=12.4 Hz), −115.50 (td, J=12.2, 7.6 Hz), −139.91 (s); ESIMS m/z 459.62 ([M+H]+).

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureat reflux with a drying tube for 12 h
  3. concentrationconcentrated in vacuo
  4. dissolutionThe crude product was dissolved in Et2O
  5. washwashed with 10% sodium thiosulfate (Na2S2O3; 2×5 mL)
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-c8b056b8d9f942bd985d29951445250a
Source dataset
uspto-grants-2014_06
Patent number
US08754229B2

Reaction notes

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