2-Bromo-6-iodo-3-methoxypyridine → HCID 86668384, compound

HRID 1466624Notes

Reaction equation

HRID 1466624 reaction equation
Br[C:2]1[C:7]([O:8][CH3:9])=[CH:6][CH:5]=[C:4]([I:10])[N:3]=1.[Cu](C#N)[C:12]#[N:13]>CN1CCCC1=O>[I:10][C:4]1[N:3]=[C:2]([C:12]#[N:13])[C:7]([O:8][CH3:9])=[CH:6][CH:5]=1

Participants

4

Reactant 2

HCID 110990402-Bromo-6-iodo-3-methoxypyridineHCID 178418260HCID 178418260, compound

Product 1

HCID 86668384HCID 86668384, compoundYield 37%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
130 °C

Procedure

To a solution of 2-bromo-6-iodo-3-methoxypyridine (627.4 mg, 1.999 mmol) in N-methylpyrrolidinone (10 mL) was added copper cyanide (202.6 mg, 2.262 mmol). The reaction mixture was stirred at 130° C. for 3.5 hours and then cooled to room temperature. The crude reaction was partitioned between ethyl acetate and water, the organic layer washed with brine, dried with magnesium sulfate, filtered, and evaporated in vacuo. The crude product was purified via flash chromatography on silica gel (20 to 100% ethyl acetate in heptanes) to yield 157.8 mg (37%) of a mixture of the two regioisomeric products 6-bromo-5-methoxypicolinonitrile and 6-iodo-3-methoxypicolinonitrile. 1H NMR (400 MHz, DMSO) δ: 8.12 (d, J=8.3 Hz, 0.75H), 7.98 (d, J=9.0 Hz, 1H), 7.80 (d, J=9.1 Hz, 1H), 7.69 (d, J=8.5 Hz, 0.75H), 3.98 (overlapping s and s, 6H).

Workup

  1. temperaturecooled to room temperature
  2. customThe crude reaction
  3. customwas partitioned between ethyl acetate and water
  4. washthe organic layer washed with brine
  5. dry with materialdried with magnesium sulfate
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customThe crude product was purified via flash chromatography on silica gel (20 to 100% ethyl acetate in heptanes)

Sources & evidence

ORD record
ord-fe1163579229406590bb2664a3a39b43
Source dataset
uspto-grants-2015_04
Patent number
US08999998B2

Reaction notes

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