Ammonium Chloride → 2-(4-Chloro-2-fluorobenzoyl)cyclopropanecarbonitrile

HRID 561454Notes

Reaction equation

HRID 561454 reaction equation
[Cl-].[Li+].[H-].C([Al+]CC(C)C)C(C)C.[Mg].Br[C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=1[F:22].[C:23]([CH:25]1[CH2:27][CH:26]1[C:28](N(OC)C)=[O:29])#[N:24].[Cl-].[NH4+]>C1COCC1>[Cl:21][C:18]1[CH:19]=[CH:20][C:15]([C:28]([CH:26]2[CH2:27][CH:25]2[C:23]#[N:24])=[O:29])=[C:16]([F:22])[CH:17]=1

Participants

8

Reactant 6

HCID 25517Ammonium ChlorideHCID 1372751-Bromo-4-chloro-2-fluorobenzeneHCID 433294Lithium ChlorideHCID 5462224MagnesiumHCID 21225700DiisobutylaluminumhydrideHCID 583925062-Cyano-N-methoxy-N-methylcyclopropanecarboxamide

Product 1

HCID 583924902-(4-Chloro-2-fluorobenzoyl)cyclopropanecarbonitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

5.67 g (134 mmol) of lithium chloride and 0.7 ml of a 0.1N solution of diisobutylaluminum hydride in THF were added to 6.50 g (268 mmol) of magnesium turnings in 30 ml of THF. The mixture was stirred for five minutes and cooled to 0° C., 22.4 g (107 mmol) of 1-bromo-4-chloro-2-fluorobenzene were added, and the mixture was allowed to warm to RT and was stirred at RT overnight. The reaction solution was added dropwise under argon to a solution of 15.0 g (97.3 mmol) of the compound from Example 73A in 10 ml of THF, and the reaction mixture was heated under reflux for 2 h. The reaction mixture was added to saturated aqueous ammonium chloride solution and extracted with dichloromethane, and the organic phase was washed with water, dried over magnesium sulfate, filtered and concentrated. The residue was purified by flash chromatography on silica gel (mobile phase: toluene/ethyl acetate 95/5) to result in 5.40 g (25% of theory) of the title compound.

Workup

  1. temperatureto warm to RT
  2. stirringwas stirred at RT overnight
  3. temperaturethe reaction mixture was heated
  4. temperatureunder reflux for 2 h
  5. extractionextracted with dichloromethane
  6. washthe organic phase was washed with water
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by flash chromatography on silica gel (mobile phase: toluene/ethyl acetate 95/5)

Sources & evidence

ORD record
ord-f3392582217b46dd8fa4daf87baae83b
Source dataset
uspto-grants-2011_11
Patent number
US08063234B2

Reaction notes

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