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

HRID 882011Notes

Reaction equation

HRID 882011 reaction equation
[NH2:1][C:2]1[C:7]([F:8])=[C:6]([C:9]2[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][CH:10]=2)[N:5]=[C:4]([C:16]([O:18][CH3:19])=[O:17])[CH:3]=1.II.[I:22](O)(=O)(=O)=O>CO>[NH2:1][C:2]1[C:7]([F:8])=[C:6]([C:9]2[CH:10]=[CH:11][C:12]([Cl:15])=[CH:13][CH:14]=2)[N:5]=[C:4]([C:16]([O:18][CH3:19])=[O:17])[C:3]=1[I:22]

Participants

5

Reactant 3

HCID 807IodineHCID 65185Metaperiodic acidHCID 70497853Methyl 4-amino-6-(4-chlorophenyl)-5-fluoropicolinate

Product 1

HCID 70498306Methyl 4-amino-6-(4-chlorophenyl)-5-fluoro-3-iodopicolinateYield 234%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A 250 mL round bottom flask was loaded with methyl 4-amino-6-(4-chlorophenyl)-5-fluoropicolinate (25 g, 0.08906 mol), iodine (18 g, 0.07125 mol), and periodic acid (H5IO6; 7.3 g, 0.03206 mol). CH3OH (100 mL) was added. The reaction mixture was stirred at reflux for 16 h. The reaction mixture was concentrated under vacuum and then dissolved in Et2O (500 mL). The ether solution was washed with 10% sodium thiosulfate (3×100 mL), water (3×100 mL) and then brine. The organic extracts were dried over anhydrous Na2SO4, filtered and concentrated under vacuum to give an orange solid. Crystallisation from EtOAc-hexane (3:7) gave a pale orange solid (30.5 g, 83%): mp 113.7-115.2° C.; 1H NMR (400 MHz, DMSO-d6) δ 7.84 (d, J=8.4 Hz, 2H), 7.55 (d, J=8.4 Hz, 2H), 6.73 (br s, 2H), 3.87 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ 167.50, 151.48 (d, JF-C=5 Hz), 145.95 (d, JF-C=13 Hz), 144.05 (d, JF-C=257 Hz), 140.75 (d, JF-C=9 Hz), 134.56, 133.42 (d, JF-C=5 Hz), 130.63 (d, JF-C=6 Hz), 129.02, 112.44 (d, JF-C=5 Hz), 77.52, 53.05; 19F NMR (376.5 MHz, DMSO-d6) δ −140.62; ESIMS m/z 407 ([M]+). Anal. Calcd. For C13H9ClFIN2O2: C, 38.40; H, 2.23; N, 6.89. Found: C, 38.40; H, 2.31; N, 6.85.

Workup

  1. temperatureat reflux for 16 h
  2. concentrationThe reaction mixture was concentrated under vacuum
  3. dissolutiondissolved in Et2O (500 mL)
  4. washThe ether solution was washed with 10% sodium thiosulfate (3×100 mL), water (3×100 mL)
  5. dry with materialThe organic extracts were dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customto give an orange solid
  9. customCrystallisation from EtOAc-hexane (3:7)

Sources & evidence

ORD record
ord-d3eb91a47c1c4fa4ae1a101427369022
Source dataset
uspto-grants-2015_03
Patent number
US08993772B2

Reaction notes

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