Hydrochloric Acid → 4-Fluoro-2-formylbenzonitrile

HRID 1966758Notes

Reaction equation

HRID 1966758 reaction equation
Br[C:2]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].C([Mg]Cl)(C)C.CN([CH:19]=[O:20])C.Cl>C1COCC1>[F:10][C:8]1[CH:7]=[CH:6][C:3]([C:4]#[N:5])=[C:2]([CH:19]=[O:20])[CH:9]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 1189392-Bromo-4-fluorobenzonitrileHCID 178418918HCID 178418918, compound

Product 1

HCID 469118144-Fluoro-2-formylbenzonitrileYield 104.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-30 °C

Procedure

To a solution of 2-bromo-4-fluorobenzonitrile (5.0 g, 25.0 mmol) in anhydrous THF (20 mL) is added iPrMgCl 2.01\4 in THF (15.0 mL, 30.0 mmol) at −30° C. The solution is stirred at −30° C. for 3 hours and DMF (5.80 mL, 75.0 mmol) is added. The reaction mixture is allowed to warm to room temperature and is stirred for 1 hour. The solution is cooled to −10° C., 2M hydrochloric acid (37 mL) is added and the solution is stirred for 20 minutes. The solution is concentrated in vacuo to −⅓ original volume and extracted into EtOAc (3×). The combined organics are then dried (Na2SO4), filtered and concentrated to afford 4-fluoro-2-formyl benzonitrile (3.9 g, 71%).

Workup

  1. temperatureto warm to room temperature
  2. stirringis stirred for 1 hour
  3. temperatureThe solution is cooled to −10° C.
  4. stirringthe solution is stirred for 20 minutes
  5. concentrationThe solution is concentrated in vacuo to −⅓ original volume
  6. extractionextracted into EtOAc (3×)
  7. dry with materialThe combined organics are then dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-229a32364a10425d908351df8bc28cba
Source dataset
uspto-grants-2013_04
Patent number
US08420655B2

Reaction notes

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