Iodine → 6-Iodo-3-(4-methoxyphenyl)-2-methylpyridine

HRID 2093173Notes

Reaction equation

HRID 2093173 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:10]=[CH:11][C:12](N)=[N:13][C:14]=2[CH3:15])=[CH:5][CH:4]=1.[I:17]I.CCCCCON=O>C(Cl)(Cl)Cl>[I:17][C:12]1[N:13]=[C:14]([CH3:15])[C:9]([C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)=[CH:10][CH:11]=1

Participants

5

Reactant 3

HCID 807IodineHCID 10026Pentyl nitriteHCID 577048485-(4-Methoxyphenyl)-6-methylpyridin-2-amine

Product 1

HCID 577048056-Iodo-3-(4-methoxyphenyl)-2-methylpyridine

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
82 °C

Procedure

5-(4-methoxyphenyl)-6-methylpyridin-2-amine (500 mg, 2.33 mmol) and iodine (710 mg, 2.8 mmol) were stirred in chloroform (10 mL) at room temperature for 12 minutes followed by addition of n-amyl nitrite (545.9 mg, 4.66 mmol). The resulting mixture was heated in a 82° C. oil bath for 1.5 hours to finish the transformation. The reaction was quenched by addition of saturated NaS2O3 aqueous solution. The reaction mixture was extracted with dichloromethane. The combined organic extracts were dried over Na2SO4 followed by filtration and concentration. The resulting crude was purified by flash column chromatography on SiO2 (Biotage 40+M cartridge, dichloromethane/hexanes, gradient) to afford a yellow oil. The oil was further purified by preparative TLC on SiO2 (eluted with 80% dichloromethane in hexanes) to afford 6-iodo-3-(4-methoxyphenyl)-2-methylpyridine. LCMS calc.=325.00; found=326.06 (M+1)+.

Workup

  1. customThe reaction was quenched by addition of saturated NaS2O3 aqueous solution
  2. extractionThe reaction mixture was extracted with dichloromethane
  3. dry with materialThe combined organic extracts were dried over Na2SO4
  4. filtrationfollowed by filtration and concentration
  5. customThe resulting crude was purified by flash column chromatography on SiO2 (Biotage 40+M cartridge, dichloromethane/hexanes, gradient)
  6. customto afford a yellow oil
  7. customThe oil was further purified by preparative TLC on SiO2 (eluted with 80% dichloromethane in hexanes)

Sources & evidence

ORD record
ord-3fa630cf1b40430a8e560916a79218e3
Source dataset
uspto-grants-2013_05
Patent number
US08440702B2

Reaction notes

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