Dimethylformamide → 2-Fluoro-5-formylbenzonitrile

HRID 1161047Notes

Reaction equation

HRID 1161047 reaction equation
[Mg].Cl[C:3]1[CH:4]=[CH:5][C:6]([F:11])=[C:7]([CH:10]=1)[C:8]#[N:9].CN(C)[CH:14]=[O:15]>O1CCCC1.II>[F:11][C:6]1[CH:5]=[CH:4][C:3]([CH:14]=[O:15])=[CH:10][C:7]=1[C:8]#[N:9]

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 936535-Chloro-2-fluorobenzonitrileHCID 5462224Magnesium

Product 1

HCID 27695822-Fluoro-5-formylbenzonitrileYield 96%

Reagents, catalysts & solvents 2

HCID 807IodineCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Add freshly ground magnesium (1.72 g, 70.7 mmol) to a solution of 5-chloro-2-fluoro-benzonitrile (10.0 g, 64.3 mmol) and N,N-dimethylformamide (5.64 g, 77.1 mmol) in tetrahydrofuran (0.2 M). Add iodine (0.816 g, 3.21 mmol). Heat the solution at reflux for 6 h. Quench the reaction with 1N hydrochloric acid and extract the mixture with ethyl acetate (3×). Dry the combined organic layers with sodium sulfate and concentrate to afford the title compound (9.20 g, 61.7 mmol, 96%): 1H NMR (CDCl3, 400 MHz) δ 7.15 (m, 1H), 7.59 (m, 1H), 7.66 (m, 1H), 10.4 (s, 1H).

Workup

  1. temperatureHeat the solution
  2. temperatureat reflux for 6 h
  3. customQuench
  4. customthe reaction with 1N hydrochloric acid
  5. extractionextract the mixture with ethyl acetate (3×)
  6. dry with materialDry the combined organic layers with sodium sulfate
  7. concentrationconcentrate

Sources & evidence

ORD record
ord-0c51cd42a64c411886bbf77300b7266e
Source dataset
uspto-grants-2010_10
Patent number
US07816523B2

Reaction notes

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