Toluene → 7-Chloro-4-(2-fluoro-4-methoxyphenyl)quinoline-2-carbonitrile

HRID 922808Notes

Reaction equation

HRID 922808 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([Cl:12])=[CH:9][CH:10]=2)[N:5]=[C:4]([C:13]#[N:14])[CH:3]=1.[F:15][C:16]1[CH:21]=[C:20]([O:22][CH3:23])[CH:19]=[CH:18][C:17]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+].C1(C)C=CC=CC=1>CCOC(C)=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:12][C:8]1[CH:7]=[C:6]2[C:11]([C:2]([C:17]3[CH:18]=[CH:19][C:20]([O:22][CH3:23])=[CH:21][C:16]=3[F:15])=[CH:3][C:4]([C:13]#[N:14])=[N:5]2)=[CH:10][CH:9]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 15789384(2-Fluoro-4-methoxyphenyl)boronic acidHCID 574378294,7-Dichloroquinoline-2-carbonitrile

Product 1

HCID 895435847-Chloro-4-(2-fluoro-4-methoxyphenyl)quinoline-2-carbonitrileYield 52.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
75 °C

Procedure

To a stirred solution of 4,7-dichloroquinoline-2-carbonitrile (6 g, 26.9 mmol), (2-fluoro-4-methoxyphenyl)boronic acid (5.03 g, 29.6 mmol), 2M sodium carbonate (29.6 ml, 59.2 mmol) in 10:1 toluene (48.9 ml) ethanol (4.89 ml) was added tetrakis(triphenylphosphine)palladium(0) (0.777 g, 0.672 mmol). The mixture was stirred at 75° C. under N2 for 18 hours. The reaction was allowed to cool to ambient temperature. The cooled reaction mixture was diluted with EtOAc and then washed with H2O, brine, dried (MgSO4) and concentrated. The residue was mostly dissolved in warm EtOAc (100 ml), added 100 ml of Et2O, allowed to stand at ambient temperature for 1 hour. The solid was collected and washed with cold Et2O (50 ml) to give 7-chloro-4-(2-fluoro-4-methoxyphenyl)quinoline-2-carbonitrile (4.4 g, 14.07 mmol, 52.3% yield) as a yellow solid.

Workup

  1. temperatureto cool to ambient temperature
  2. customThe cooled reaction mixture
  3. washwashed with H2O, brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. dissolutionThe residue was mostly dissolved in warm EtOAc (100 ml)
  7. additionadded 100 ml of Et2O
  8. waitto stand at ambient temperature for 1 hour
  9. customThe solid was collected
  10. washwashed with cold Et2O (50 ml)

Sources & evidence

ORD record
ord-043c0f46d0a242ee9fa78391287e62b8
Source dataset
uspto-grants-2016_03
Patent number
US09278960B2

Reaction notes

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