Isoamyl Nitrite → 3-Iodo-2-methyl-6-(trifluoromethyl)pyridine

HRID 604608Notes

Reaction equation

N[C:2]1[C:3]([CH3:12])=[N:4][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:6][CH:7]=1.N(OCCC(C)C)=O.[I-:21]>C(Cl)(Cl)Cl>[I:21][C:2]1[C:3]([CH3:12])=[N:4][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 3-amino-2-methyl-6-(trifluoromethyl)pyridine (500 mg, 2.84 mmol), isoamyl nitrite 760 μL, 5.68 mmol) and iodide. (793 mg, 3.12 mmol) in dry CHCl3 (10 mL) was stirred at room temperature for 0.5 h. The mixture was heated at 80° C. under N2 for 4 h. The reaction mixture was quenched with saturated Na2S2O3 then partitioned between CH2Cl2 and water. The organic layer was dried (Na2SO4) and concentrated in vacuo. The residue was purified by flash chromatography (Si, 1% EtOAc in hexanes) to afford 3-iodo-2-methyl-6-(trifluoromethyl)pyridine. LCMS calc.=288.0; found=288.0 (M+1)+. 1H NMR (500 MHz, CDCl3) δ 8.25 (d, J=8.0 Hz, 1H); 7.22 (d, J=8.1 Hz, 1H); 2.83 (s, 3H).

Workup

customThe reaction mixture was quenched with saturated Na2S2O3
customthen partitioned between CH2Cl2 and water
dry with materialThe organic layer was dried (Na2SO4)
concentrationconcentrated in vacuo
customThe residue was purified by flash chromatography (Si, 1% EtOAc in hexanes)

Sources & evidence

ORD record: ord-21869445d738483aa3519101db350f49
Source dataset: uspto-grants-2011_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07910592B2

Reaction notes

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