Ammonium Chloride → 2-(2,4-Difluorobenzoyl)cyclopropanecarbonitrile

HRID 561448Notes

Reaction equation

HRID 561448 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1Br.[Mg].[C:11]([CH:13]1[CH2:15][CH:14]1[C:16](N(OC)C)=[O:17])#[N:12].[Cl-].[NH4+]>BrC(Br)C.C(OCC)C.C1COCC1>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:16]([CH:14]1[CH2:15][CH:13]1[C:11]#[N:12])=[O:17]

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 676741-Bromo-2,4-difluorobenzeneHCID 5462224MagnesiumHCID 583925062-Cyano-N-methoxy-N-methylcyclopropanecarboxamide

Product 1

HCID 583925512-(2,4-Difluorobenzoyl)cyclopropanecarbonitrile

Reagents, catalysts & solvents 3

HCID 112011,1-DibromoethaneCatalystHCID 3283Diethyl EtherSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

Under argon, a few drops of dibromoethane and then 5.00 g (25.9 mmol) of 2,4-difluorobromobenzene, dissolved in 50 ml of diethyl ether, were added to 661 mg (27.2 mmol) of magnesium in 100 ml of dry diethyl ether. The mixture was heated under reflux for 2 h. After cooling, the supernatant reaction solution was added dropwise under argon to a solution of 3.63 g (23.5 mmol) of the compound from Example 73A in 80 ml of THF, and the mixture was stirred at RT overnight. The reaction solution was then added to saturated aqueous ammonium chloride solution and extracted with dichloromethane. The organic phase was dried over magnesium sulfate, filtered and concentrated. Purification of the residue by flash chromatography on silica gel (mobile phase: toluene/ethyl acetate gradient) resulted in 2.15 g (44% of theory) of the title compound.

Workup

  1. temperatureThe mixture was heated
  2. temperatureunder reflux for 2 h
  3. temperatureAfter cooling
  4. extractionextracted with dichloromethane
  5. dry with materialThe organic phase was dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification of the residue by flash chromatography on silica gel (mobile phase: toluene/ethyl acetate gradient)

Sources & evidence

ORD record
ord-1885f70691ee4fb9b7ced9b1d96b380d
Source dataset
uspto-grants-2011_11
Patent number
US08063234B2

Reaction notes

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