Sodium Carbonate → 5-(2-Chloro-4-methoxy-phenyl)-2-trifluoromethylisonicotinonitrile

HRID 1891381Notes

Reaction equation

HRID 1891381 reaction equation
Br[C:2]1[C:7]([C:8]#[N:9])=[CH:6][C:5]([C:10]([F:13])([F:12])[F:11])=[N:4][CH:3]=1.[Cl:14][C:15]1[CH:20]=[C:19]([O:21][CH3:22])[CH:18]=[CH:17][C:16]=1B(O)O.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.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:14][C:15]1[CH:20]=[C:19]([O:21][CH3:22])[CH:18]=[CH:17][C:16]=1[C:2]1[C:7]([C:8]#[N:9])=[CH:6][C:5]([C:10]([F:13])([F:12])[F:11])=[N:4][CH:3]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27733302-Chloro-4-methoxybenzeneboronic acidHCID 569733155-Bromo-2-(trifluoromethyl)isonicotinonitrile

Product 1

HCID 684720965-(2-Chloro-4-methoxy-phenyl)-2-trifluoromethylisonicotinonitrileYield 41.9%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

To a mixture of 5-bromo-2-trifluoromethyl-isonicotinonitrile 1-1 (2.51 g, mmol) in dioxane (3.3 mL) and water (3.3 mL), were added 2-chloro-4-methoxyphenylboronic acid (2.3 g, 12.5 mmol) and Na2CO3 (6.3 g). The mixture was purged with nitrogen gas for 10 min, then Pd(PPh3)4 (1.2 g, 1.0 mmol) was added. The mixture was stirred in a sealed vessel at 85° C. for 6 hrs, then extracted by ethyl acetate. The organic layer was washed with water, dried over MgSO4. Concentration and purification by silica gel column chromatography eluting with hexane/ethyl acetate (10/1) yielded 5-(2-chloro-4-methoxy-phenyl)-2-trifluoromethylisonicotinonitrile (1.31 g). tR=2.96 min (method 1).

Workup

  1. customThe mixture was purged with nitrogen gas for 10 min
  2. extractionextracted by ethyl acetate
  3. washThe organic layer was washed with water
  4. dry with materialdried over MgSO4
  5. concentrationConcentration and purification by silica gel column chromatography
  6. washeluting with hexane/ethyl acetate (10/1)

Sources & evidence

ORD record
ord-2f8bd823c1214139bfda4fc11f79a411
Source dataset
uspto-grants-2013_08
Patent number
US08507536B2

Reaction notes

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