Dichloromethane → 4'-Amino-3-fluoro-3'-nitro-[1,1'-biphenyl]-4-carbonitrile

HRID 1424224Notes

Reaction equation

HRID 1424224 reaction equation
Br[C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([N+:9]([O-:11])=[O:10])[CH:3]=1.[C:12]([C:14]1[CH:19]=[CH:18][C:17](B(O)O)=[CH:16][C:15]=1[F:23])#[N:13].C(=O)([O-])[O-].[Na+].[Na+].ClCCl>O.O1CCCC1.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Fe]>[NH2:6][C:5]1[CH:7]=[CH:8][C:2]([C:17]2[CH:18]=[CH:19][C:14]([C:12]#[N:13])=[C:15]([F:23])[CH:16]=2)=[CH:3][C:4]=1[N+:9]([O-:11])=[O:10]

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 701324-Bromo-2-nitroanilineHCID 2783130(4-Cyano-3-fluorophenyl)boronic acid

Product 1

HCID 866991344'-Amino-3-fluoro-3'-nitro-[1,1'-biphenyl]-4-carbonitrileYield 65%

Reagents, catalysts & solvents 3

HCID 178477754HCID 178477754, compoundCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of 4-bromo-2-nitroaniline (5.02 g, 23.1 mmol), 4-cyano-3-fluorophenylboronic acid (3.62 g, 21.9 mmol), and sodium carbonate (6.1 g, 58 mmol) in water (10 mL) and tetrahydrofuran (35 mL) was sparged with nitrogen for 10 minutes. To this was added [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (0.42 g, 0.51 mmol). The reaction mixture was heated at 65° C. for 6 hours. The mixture was allowed to cool, concentrated in vacuo, diluted with ethyl acetate, washed with saturated aqueous sodium hydrogen carbonate, water and brine. The organic layer was dried over anhydrous magnesium sulphate, filtered, and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with a 0-100% ethyl acetate/hexanes gradient to afford the title compound (3.64 g, 65%) as a yellow solid.

Workup

  1. customwas sparged with nitrogen for 10 minutes
  2. temperatureto cool
  3. concentrationconcentrated in vacuo
  4. additiondiluted with ethyl acetate
  5. washwashed with saturated aqueous sodium hydrogen carbonate, water and brine
  6. dry with materialThe organic layer was dried over anhydrous magnesium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified
  10. washeluting with a 0-100% ethyl acetate/hexanes gradient

Sources & evidence

ORD record
ord-5b15dbf40c674c86aac29780f14131ec
Source dataset
uspto-grants-2015_01
Patent number
US08927587B2

Reaction notes

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