Sodium Carbonate → 6-Fluoro-3,4-dimethoxy-2-(2-pyridyl)benzonitrile

HRID 1582379Notes

Reaction equation

HRID 1582379 reaction equation
[F:1][C:2]1[C:7]([C:8]#[N:9])=[C:6](I)[C:5]([O:11][CH3:12])=[C:4]([O:13][CH3:14])[CH:3]=1.B([O-])O[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=1.C(=O)([O-])[O-].[Na+].[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>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.[Cu]I.O.C(OCC)(=O)C.O1CCOCC1>[F:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=2)[C:5]([O:11][CH3:12])=[C:4]([O:13][CH3:14])[CH:3]=1

Participants

10

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 227212146-Fluoro-2-iodo-3,4-dimethoxybenzonitrileHCID 178514833HCID 178514833, compound

Product 1

HCID 98138056-Fluoro-3,4-dimethoxy-2-(2-pyridyl)benzonitrileYield 48%

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

Stirred dioxane (20 ml) at 80° C. was charged with 6-fluoro-2-iodo-3,4-dimethoxybenzonitrile from Example 1(a) (1.0 g, 3.3 mmol), tetrakis(triphenylphosphine)palladium(0) (0.19 g, 0.16 mmol), the pyridyl boronate from step (a) above (6.1 g, estimated to be 9.9 mmol), copper(I)iodide (0.25 g, 1.3 mmol), sodium carbonate (0.69 g, 6.5 mmol) and triphenylphosphine (0.17 g, 0.65 mmol) and the resulting brown slurry heated to reflux and stirred at this temperature overnight. The resulting suspension was cooled to room temperature, ethyl acetate (20 ml) and water (10 ml) added and the resulting mixture filtered through Arbocel™ filter aid. The phases were separated and the aqueous phase extracted with ethyl acetate (2×20 ml). The organic phases were combined, washed with saturated aqueous NaCl and stripped to an oil. Acetonitrile was added and the mixture warmed then cooled. The resulting suspension was filtered to give a solid that was dried in vacuo overnight at 45° C. to give 0.419 of the product (48%).

Workup

  1. temperatureto reflux
  2. filtrationthe resulting mixture filtered through Arbocel™
  3. filtrationfilter aid
  4. customThe phases were separated
  5. extractionthe aqueous phase extracted with ethyl acetate (2×20 ml)
  6. washwashed with saturated aqueous NaCl
  7. additionAcetonitrile was added
  8. temperaturethe mixture warmed
  9. temperaturethen cooled
  10. filtrationThe resulting suspension was filtered
  11. customto give a solid
  12. customthat was dried in vacuo overnight at 45° C.

Sources & evidence

ORD record
ord-b95961a7c2bb411b993ce02ce68a7f5e
Source dataset
uspto-grants-2004_05
Patent number
US06734303B2

Reaction notes

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