Dimethylformamide → 3-Fluoro-5-methoxy-4-nitrobenzonitrile

HRID 511352Notes

Reaction equation

HRID 511352 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:12][CH3:13])[C:5]([N+:9]([O-:11])=[O:10])=[C:6]([F:8])[CH:7]=1.[CH3:14][N:15](C=O)C>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.[C-]#N.[Zn+2].[C-]#N>[F:8][C:6]1[CH:7]=[C:2]([CH:3]=[C:4]([O:12][CH3:13])[C:5]=1[N+:9]([O-:11])=[O:10])[C:14]#[N:15]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 579556485-Bromo-3-fluoro-2-nitroanisole

Product 1

HCID 579555403-Fluoro-5-methoxy-4-nitrobenzonitrileYield 84%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Procedure

Into a microwave vial was added 5-bromo-1-fluoro-3-methoxy-2-nitrobenzene (1.75 g, 7.00 mmol), Pd(PPh3)4 (1.132 g, 0.9798 mmol), and zinc cyanide (0.8222 g, 7.002 mmol). The vial was sealed, and then DMF (28 mL) was added. The vial was evacuated and purged with N2 gas (3 times). The reaction mixture was irradiated on the microwave for 3-5 minutes at 150° C. The reaction mixture was quenched with water (30 mL) and then extracted with EtOAc (60 mL). The organic layer was washed with water (30 mL), brine (2×20 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to yield a yellow oil. The crude material was purified by silica gel chromatography on an ISCO combi-flash Rf system using Heptane/EtOAc (100:0→55:45) as eluent to yield the desired product as a light yellow solid 1.15 g (84% yield). 1H NMR (CDCl3, 400 MHz): δ=4.01 (s, 3 H), 7.14 (t, J=1.52 Hz, 1 H), 7.19 (dd, J=8.21, 1.39 Hz, 1 H).

Workup

  1. customThe vial was sealed
  2. customThe vial was evacuated
  3. custompurged with N2 gas (3 times)
  4. customThe reaction mixture was irradiated on the microwave for 3-5 minutes at 150° C
  5. customThe reaction mixture was quenched with water (30 mL)
  6. extractionextracted with EtOAc (60 mL)
  7. washThe organic layer was washed with water (30 mL), brine (2×20 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customto yield a yellow oil
  12. customThe crude material was purified by silica gel chromatography on an ISCO combi-flash Rf system

Sources & evidence

ORD record
ord-6a5335d1e8874beea9dd59ea4aa1caab
Source dataset
uspto-grants-2015_08
Patent number
US09096624B2

Reaction notes

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