6-Bromo-3,5-dimethoxypicolinonitrile → 6-Ethyl-3,5-dimethoxy-pyridine-2-carbonitrile

HRID 1500647Notes

Reaction equation

HRID 1500647 reaction equation
Br[C:2]1[N:7]=[C:6]([C:8]#[N:9])[C:5]([O:10][CH3:11])=[CH:4][C:3]=1[O:12][CH3:13].[CH2:14]([Mg]Br)[CH3:15]>O1CCCC1.[Ni](Cl)Cl.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:14]([C:2]1[N:7]=[C:6]([C:8]#[N:9])[C:5]([O:10][CH3:11])=[CH:4][C:3]=1[O:12][CH3:13])[CH3:15]

Participants

5

Reactant 2

HCID 735549116-Bromo-3,5-dimethoxypicolinonitrileHCID 178418443HCID 178418443, compound

Product 1

HCID 669867776-Ethyl-3,5-dimethoxy-pyridine-2-carbonitrile

Reagents, catalysts & solvents 2

HCID 2724937Dichloro(1,1'-(1,3-propanediyl)bis(1,1-diphenylphosphine-kappaP))nickelCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Impure 6-bromo-3,5-dimethoxy-pyridine-2-carbonitrile (462 mg; <1.9 mmol) was dissolved in tetrahydrofuran (20 mL) under nitrogen, and to the solution was added 1,3-bis(diphenylphosphino)propane nickel (II) chloride (105 mg; 0.19 mmol). The solution was cooled to 0° C., and a solution of ethyl magnesium bromide (1.0 molar in THF; 2.7 mL; 1.4 eq.) was slowly added. The reaction was stirred for five minutes, and quenched with saturated aqueous ammonium chloride (10 mL). To the reaction was added ethyl acetate (40 mL) and water (40 mL). The organic layer was isolated, dried over sodium sulfate, evaporated, and purified by column chromatography to give 6-ethyl-3,5-dimethoxy-pyridine-2-carbonitrile (114 mg; 0.6 mmol).

Workup

  1. customquenched with saturated aqueous ammonium chloride (10 mL)
  2. additionTo the reaction was added ethyl acetate (40 mL) and water (40 mL)
  3. customThe organic layer was isolated
  4. dry with materialdried over sodium sulfate
  5. customevaporated
  6. custompurified by column chromatography

Sources & evidence

ORD record
ord-d71aed611de44723a7f3ab8c9b9cf1c6
Source dataset
uspto-grants-2015_12
Patent number
US09206162B2

Reaction notes

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