Iodine → Methyl 4-amino-6-(4-chloro-3-fluorophenyl)-5-fluoro-3-iodopicolinate

HRID 244322Notes

Reaction equation

HRID 244322 reaction equation
[NH2:1][C:2]1[C:7]([F:8])=[C:6]([C:9]2[CH:14]=[CH:13][C:12]([Cl:15])=[C:11]([F:16])[CH:10]=2)[N:5]=[C:4]([C:17]([O:19][CH3:20])=[O:18])[CH:3]=1.[I:21](O)(=O)(=O)=O.II>CO.ClCCl>[NH2:1][C:2]1[C:7]([F:8])=[C:6]([C:9]2[CH:14]=[CH:13][C:12]([Cl:15])=[C:11]([F:16])[CH:10]=2)[N:5]=[C:4]([C:17]([O:19][CH3:20])=[O:18])[C:3]=1[I:21]

Participants

6

Reactant 3

HCID 807IodineHCID 65185Metaperiodic acidHCID 70498547Methyl 4-amino-6-(4-chloro-3-fluorophenyl)-5-fluoropicolinate

Product 1

HCID 70497132Methyl 4-amino-6-(4-chloro-3-fluorophenyl)-5-fluoro-3-iodopicolinateYield 236.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

Methyl 4-amino-6-(4-chloro-3-fluorophenyl)-5-fluoropicolinate (3.1 g, 10.38 mmol) was dissolved in methanol (40 mL). Periodic acid (0.946 g, 4.15 mmol) and iodine (2.371 g, 9.34 mmol) were added. The reaction mixture was heated at reflux overnight. The cooled reaction mixture was diluted with dichloromethane and washed with 1N sodium sulfite. The organic phase was washed with 1N sodium sulfite, washed with saturated sodium chloride, dried over magnesium sulfate, fitered, and concentrated onto celite. The product was purified by flash chromatography (SiO2, 100% dichloromethane) to provide the title compound 4.17 g, 9.82 mmol, 95% yield) as a pink solid: 1H NMR (400 MHz, DMSO-d6) d 3.88 (s, 3H), 6.80 (s, 2H), 7.65-7.77 (m, 2H), 7.77-7.84 (m, 1H); 19F NMR (376 MHz, DMSO-d6) d −140.15 , −115.85. ESIMS m/z 426 ([M+H]+).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux overnight
  3. customThe cooled reaction mixture
  4. washwashed with 1N sodium sulfite
  5. washThe organic phase was washed with 1N sodium sulfite
  6. washwashed with saturated sodium chloride
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated onto celite
  9. customThe product was purified by flash chromatography (SiO2, 100% dichloromethane)

Sources & evidence

ORD record
ord-1dec098e02994440a2f2b2c59900d529
Source dataset
uspto-grants-2014_02
Patent number
US08658568B2

Reaction notes

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