Dimethylformamide → 4-Methoxypyrimidine-2-carbonitrile

HRID 2070968Notes

Reaction equation

HRID 2070968 reaction equation
Cl[C:2]1[N:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][N:3]=1.[CH3:10][N:11](C=O)C>CCOC(C)=O.[C-]#N.[Zn+2].[C-]#N>[CH3:9][O:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([C:10]#[N:11])[N:7]=1

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 5889352-Chloro-4-methoxypyrimidine

Product 1

HCID 132211894-Methoxypyrimidine-2-carbonitrileYield 50%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

2-chloro-4-methoxypyrimidine (500 mg, 3.45 mmol) was combined with zinc cyanide (242 mg, 2.07 mmol) and tetrakis (triphenylphosphne)palladium (0) (159 mg, 0.14 mmol) in DMF (10 mL) and the slurry was heated at 80° C. under nitrogen for 6 h. The mixture was cooled to rt, diluted with EtOAc (50 mL) and washed twice with 2N ammonium hydroxide (50 mL). The EtOAc solution was washed with brine (20 mL) and concentrated in vacuo to provide the crude mixture. The crude was then purified by column chromatography (10% EtOAc in hexanes) to afford 4-methoxypyrimidine-2-carbonitrile in 50% yield.

Workup

  1. temperatureThe mixture was cooled to rt
  2. washwashed twice with 2N ammonium hydroxide (50 mL)
  3. washThe EtOAc solution was washed with brine (20 mL)
  4. concentrationconcentrated in vacuo
  5. customto provide the crude mixture
  6. customThe crude was then purified by column chromatography (10% EtOAc in hexanes)

Sources & evidence

ORD record
ord-5652bc9d87534e43b4a20f2015bb210b
Source dataset
uspto-grants-2012_10
Patent number
US08299267B2

Reaction notes

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