Dimethylformamide → 2-Fluoro-5-(methylamino)-4-nitrobenzonitrile

HRID 1048996Notes

Reaction equation

HRID 1048996 reaction equation
Br[C:2]1[C:3]([F:13])=[CH:4][C:5]([N+:10]([O-:12])=[O:11])=[C:6]([NH:8][CH3:9])[CH:7]=1.[CH3:14][N:15](C=O)C>[Cl-].[NH4+].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].[C-]#N.[Zn+2].[C-]#N>[F:13][C:3]1[CH:4]=[C:5]([N+:10]([O-:12])=[O:11])[C:6]([NH:8][CH3:9])=[CH:7][C:2]=1[C:14]#[N:15]

Participants

7

Reactant 2

HCID 6228DimethylformamideHCID 66685077HCID 66685077, compound

Product 1

HCID 666848852-Fluoro-5-(methylamino)-4-nitrobenzonitrile

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
120 °C

Procedure

A stirred solution of (5-Bromo-4-fluoro-2-nitro-phenyl)-methyl-amine (0.5 g, 0.0020 mol) in DMF (10 ml) was purged with Argon for 15 min. To the above mixture, Pd2(dba)3 (0.09 g, 0.001 mol), dppf (0.13 g, 0.0024 mol), and zinc cyanide (0.14 g, 0.0012 mol) was added carefully under argon atmosphere. The reaction mixture was heated at 120° C. for 22 h. Cooled to RT, diluted with saturated solution of ammonium chloride, filtered through CELITE® and the filter bed was thoroughly washed with ethyl acetate. The resulting mixture was separated, organic layer was washed with water, brine, dried over Na2SO4, filtered and concentrated under vacuum to afford the crude compound, which was purified by column chromatography to obtain title compound 2-fluoro-5-methylamino-4-nitro-benzonitrile as a brick red solid. C8H6FN3O2; 1H NMR (400 MHz, CdCl3) δ 8.04 (d, J=9.2 Hz, 1H), 7.85 (brs, 1H), 7.11 (d, J=4.8 Hz, 1H), 3.05 (d, J=4.8 Hz, 3H). MS (M+1): 195.1.

Workup

  1. temperatureCooled to RT
  2. filtrationfiltered through CELITE®
  3. washthe filter bed was thoroughly washed with ethyl acetate
  4. customThe resulting mixture was separated
  5. washorganic layer was washed with water, brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum
  9. customto afford the crude compound, which
  10. customwas purified by column chromatography

Sources & evidence

ORD record
ord-e4cfc35e8b7a40c8a35a982e0b034da2
Source dataset
uspto-grants-2016_07
Patent number
US09382226B2

Reaction notes

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