Methyl iodide → 5-Bromo-3-(difluoromethoxy)-2-methoxypyridine

HRID 39356Notes

Reaction equation

HRID 39356 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([O:9][CH:10]([F:12])[F:11])[C:5]([OH:8])=[N:6][CH:7]=1.[CH3:13]I>C(Cl)(Cl)Cl.C(=O)([O-])[O-].[Ag+2]>[Br:1][C:2]1[CH:3]=[C:4]([O:9][CH:10]([F:12])[F:11])[C:5]([O:8][CH3:13])=[N:6][CH:7]=1

Participants

5

Reactant 2

HCID 6328Methyl iodideHCID 178517597HCID 178517597, compound

Product 1

HCID 666175125-Bromo-3-(difluoromethoxy)-2-methoxypyridine

Reagents, catalysts & solvents 2

HCID 178418647HCID 178418647, compoundCatalystHCID 6212ChloroformSolvent

Procedure

As shown in step 3-v of Scheme 3, 5-bromo-3-(difluoromethoxy)pyridin-2-ol (300 mg; 1.25 mmol) was dissolved in 5 mL of chloroform. Silver carbonate (690 mg; 2.5 mmol) and methyl iodide (780 μL; 1.77 g; 12.5 mmol) were added and the mixture stirred at RT overnight. The reaction mixture was filtered through diatomaceous earth, which was washed with additional CHCl3. The filtrates were concentrated under reduced pressure to yield an oil which was purified by silica gel chromatography to yield 5-bromo-3-(difluoromethoxy)-2-methoxypyridine as a white solid (Compound 1010, 250 mg, 78% yield): ESMS (M+H) 254/256; 1H NMR (CDCl3) δ 8.08 (d, 1H, J=2.1 Hz), 7.56 (d, 1H, J=2.1 Hz), 6.60 (t, 1H, J=75 Hz), 3.98 (s, 3H).

Workup

  1. filtrationThe reaction mixture was filtered through diatomaceous earth, which
  2. washwas washed with additional CHCl3
  3. concentrationThe filtrates were concentrated under reduced pressure
  4. customto yield an oil which
  5. customwas purified by silica gel chromatography

Sources & evidence

ORD record
ord-77e759ac61c04ffa90566f6f944f0eb4
Source dataset
uspto-grants-2013_09
Patent number
US08524906B2

Reaction notes

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