Iodine → HCID 118600341, compound

HRID 1508528Notes

Reaction equation

HRID 1508528 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1[C:10]1[N:15]=[CH:14][C:13]([C:16]([O:18][CH3:19])=[O:17])=[C:12]([C:20]([F:23])([F:22])[F:21])[CH:11]=1.[I:24]I>S([O-])([O-])(=O)=O.[Ag+2].[O-]S([O-])(=O)=O.[Ag+].[Ag+].CO>[F:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[C:5]([I:24])=[CH:4][C:3]=1[C:10]1[N:15]=[CH:14][C:13]([C:16]([O:18][CH3:19])=[O:17])=[C:12]([C:20]([F:23])([F:21])[F:22])[CH:11]=1

Participants

6

Reactant 2

HCID 807Iodine2×HCID 67513426HCID 67513426, compound

Product 1

HCID 118600341HCID 118600341, compound

Reagents, catalysts & solvents 3

HCID 159865Silver sulfateCatalystHCID 178418844HCID 178418844, compoundCatalystHCID 887MethanolSolvent

Procedure

Methyl 6-(2-fluoro-4-methoxyphenyl)-4-(trifluoromethyl)pyridine-3-carboxylate (750 mg, 2.278 mmol), iodine (578 mg, 2.278 mmol), silver sulfate (710 mg, 2.278 mmol) and MeOH (20 mL) were stirred in a 70° C. oil bath and monitored by LCMS. The dark color disappeared and LCMS indicated >50% conversion when reaction time=1 hr. Additional I2 (280 mg, 0.788 mmol) and Ag2SO4 (355 mg, 1.074 mmol) were added and resumed stirring/heating for 30 min. The reaction was cooled and quenched by adding Na2S2O3 (sat.). Volatiles were removed under reduced pressure. The pot residue was worked up with brine, extracted with ethyl acetate, dried over Na2SO4, filtered and evaporated in vacuo. The resulting mixture was purified by flash chromatography (SiO2, Biotage SNAP Cartridge, silica gel, KP-Sil, 100 g cartridge). The column was eluted by an EtOAc/hexanes mixture (0% to 40%). Pure fractions were pooled and evaporated to afford a white solid as the titled compound. LCMS calc.=454.96. found=456.03 (M+H)+. 1H NMR (CDCl3, 600 MHz) δ 9.15 (s, 1H), 8.61 (d, J=9.0 Hz, 1H), 8.11 (s, 1H), 6.68 (d, J=11.0, 1H), 4.00 (s, 3H), 3.96 (s, 3H).

Workup

  1. custom>50% conversion when reaction time=1 hr
  2. temperatureresumed stirring/heating for 30 min
  3. temperatureThe reaction was cooled
  4. customquenched
  5. additionby adding Na2S2O3 (sat.)
  6. customVolatiles were removed under reduced pressure
  7. extractionextracted with ethyl acetate
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. customevaporated in vacuo
  11. customThe resulting mixture was purified by flash chromatography (SiO2, Biotage SNAP Cartridge, silica gel, KP-Sil, 100 g cartridge)
  12. washThe column was eluted by an EtOAc/hexanes mixture (0% to 40%)
  13. customevaporated

Sources & evidence

ORD record
ord-fafcb56957054caa84a3e05c1dbd9e2c
Source dataset
uspto-grants-2015_12
Patent number
US09221834B2

Reaction notes

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