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

HRID 2382704Notes

Reaction equation

HRID 2382704 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, 10 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-7da563a61d2444f78d979c0e6435cc1b
Source dataset
uspto-grants-2012_09
Patent number
US08263588B2

Reaction notes

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