Dimethylformamide → 6-Chloro-4-methoxypyridine-3-carbonitrile

HRID 1187049Notes

Reaction equation

HRID 1187049 reaction equation
Br[C:2]1[C:3]([O:9][CH3:10])=[CH:4][C:5]([Cl:8])=[N:6][CH:7]=1.[CH3:11][N:12](C=O)C>[C-]#N.[C-]#N.[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:8][C:5]1[N:6]=[CH:7][C:2]([C:11]#[N:12])=[C:3]([O:9][CH3:10])[CH:4]=1

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 498534155-Bromo-2-chloro-4-methoxypyridine

Product 1

HCID 547588416-Chloro-4-methoxypyridine-3-carbonitrile

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
95 °C

Procedure

A solution of 5-bromo-2-chloro-4-methoxypyridine (5.0 g, 22.48 mmol) in DMF (80 mL) was purged with nitrogen for 15 min. At this point, Zn(CN)2 (3.96 g, 33.7 mmol) and Pd(Ph3P)4 (2.60 g, 2.25 mmol) were added, successively. The resulting suspension was stirred at 95° C. for 12 h under nitrogen atm. The reaction mixture was cooled to ambient temperature, filtered to remove inorganic solid. The solvent (DMF) was evaporated to provide the crude residue as an oil, which was purified on silica gel and eluted with 0-30% ethyl acetate/hexanes to afford the product. 1H NMR (500 MHz, DMSO-d6), δ 8.69 (s, 1H), 7.50 (s, 1H), 4.04 (s, 3H);

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. filtrationfiltered
  3. customto remove inorganic solid
  4. customThe solvent (DMF) was evaporated

Sources & evidence

ORD record
ord-1141ed3b11fc4d58abeb3e7de7e7fea2
Source dataset
uspto-grants-2014_03
Patent number
US08673920B2

Reaction notes

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