Dimethylformamide → 2,4-Difluoro-3-formylbenzonitrile

HRID 1610137Notes

Reaction equation

HRID 1610137 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[F:13][C:14]1[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:15]=1[C:16]#[N:17].CN(C)[CH:25]=[O:26]>CCCCCC.O1CCCC1.O.C(O)(=O)C>[F:13][C:14]1[C:21]([CH:25]=[O:26])=[C:20]([F:22])[CH:19]=[CH:18][C:15]=1[C:16]#[N:17]

Participants

9

Reactant 4

HCID 6228DimethylformamideHCID 7912DiisopropylamineHCID 775452,4-DifluorobenzonitrileHCID 178418339Butyllithium

Product 1

HCID 106071732,4-Difluoro-3-formylbenzonitrile

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

In an atmosphere of nitrogen gas, 66 ml of a 1.6 M solution of n-butyllithium in hexane was added to an ice-cold solution of 11.1 g of N,N-diisopropylamine in 100 ml tetrahydrofuran, and the mixture was stirred at the same temperature for 20 minutes. After cooling to −78° C., a solution of 13.9 g of 2,4-difluorobenzonitrile in 15 ml tetrahydrofuran was added dropwise. After stirring at the same temperature for 10 minutes, 8.6 ml of dimethylformamide was added dropwise and the mixture was stirred at the same temperature for 15 minutes. After adding 20 ml of glacial acetic acid to the reaction mixture, 200 ml of water was added and the mixture was extracted with diethyl ether for two times. The organic layer was sequentially washed with 0.2 N hydrochloric acid and brine, dried over anhydrous magnesium sulfate and the solvent was evaporated. The resulting crude crystals were triturated with diethyl ether-n-hexane, to give 8.61 g of the title compound as bright yellow crystals.

Workup

  1. stirringAfter stirring at the same temperature for 10 minutes
  2. stirringthe mixture was stirred at the same temperature for 15 minutes
  3. additionwas added
  4. extractionthe mixture was extracted with diethyl ether for two times
  5. washThe organic layer was sequentially washed with 0.2 N hydrochloric acid and brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customthe solvent was evaporated
  8. customThe resulting crude crystals were triturated with diethyl ether-n-hexane

Sources & evidence

ORD record
ord-189d4c8819c640a8a36d07b799825843
Source dataset
uspto-grants-2006_01
Patent number
US06982274B2

Reaction notes

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