Iodine → 5-Iodo-4-methyl-2-(trifluoromethyl)pyridine

HRID 604639Notes

Reaction equation

HRID 604639 reaction equation
N(OCCC(C)C)=O.[CH3:9][C:10]1[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[N:13]=[CH:12][C:11]=1N.[I:21]I>C(Cl)(Cl)Cl>[I:21][C:11]1[C:10]([CH3:9])=[CH:15][C:14]([C:16]([F:19])([F:18])[F:17])=[N:13][CH:12]=1

Participants

5

Reactant 3

HCID 807IodineHCID 8053Isoamyl NitriteHCID 497579514-Methyl-6-(trifluoromethyl)pyridin-3-amine

Product 1

HCID 670577315-Iodo-4-methyl-2-(trifluoromethyl)pyridine

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Procedure

Isoamyl nitrite (96%, 59 μL, 49.9 mg, 0.426 mmol) was added to a solution of 4-methyl-6-(trifluoromethyl)pyridin-3-amine (50.0 mg, 0.284 mmol) and iodine (79.2 mg, 0.312 mmol) in CHCl3 (1 mL) at room temperature under N2. The solution was stirred for 5 min then heated at reflux for 2 h. The reaction mixture was diluted with CHCl3, washed with saturated Na2SO3, dried (MgSO4) and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Si, 12×160 mm, 1-5% EtOAc in hexanes gradient) to afford 5-iodo-4-methyl-2-(trifluoromethyl)pyridine. Rf=0.77 (10% EtOAc/hexanes). LCMS calc.=288.0; found=288.0 (M+1)+. 1H NMR (600 MHz, CDCl3): δ 8.96 (s, 1H); 7.54 (s, 1H); 2.50 (s, 3H).

Workup

  1. temperaturethen heated
  2. temperatureat reflux for 2 h
  3. washwashed with saturated Na2SO3
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customto give the crude product
  7. customThis was purified by flash chromatography (Si, 12×160 mm, 1-5% EtOAc in hexanes gradient)

Sources & evidence

ORD record
ord-6df6d686b1a64f89a6635283569edce5
Source dataset
uspto-grants-2011_03
Patent number
US07910592B2

Reaction notes

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