1-Bromo-2-Chloroethane → 1-(4-Bromo-2-fluorophenyl)cyclopropane-1-carbonitrile

HRID 1423996Notes

Reaction equation

HRID 1423996 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]#[N:10])=[C:4]([F:11])[CH:3]=1.Br[CH2:13][CH2:14]Cl.[OH-].[K+]>[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1.O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:9]#[N:10])[CH2:14][CH2:13]2)=[C:4]([F:11])[CH:3]=1

Participants

6

Reactant 3

HCID 78491-Bromo-2-ChloroethaneHCID 14797Potassium HydroxideHCID 71723082-(4-Bromo-2-fluorophenyl)acetonitrile

Product 1

HCID 587623291-(4-Bromo-2-fluorophenyl)cyclopropane-1-carbonitrileYield 438.7%

Reagents, catalysts & solvents 2

HCID 66133Benzyl triethylammonium chlorideCatalystHCID 962WaterSolvent

Procedure

A solution of the compound (22.6 g, 23.36 mmol) obtained in Example 14-1), 1-bromo-2-chloroethane (18.9 g, 132 mmol), benzyltriethylammonium chloride (0.48 g, 2.34 mmol), and potassium hydroxide (41.5 g, 739 mmol) in water (40 mL) was stirred at 40° C. for 9 h. The reaction mixture was cooled to room temperature and extracted with ethyl acetate, and the organic layer was washed with water, a 1 M aqueous hydrochloric acid solution, and saturated sodium chloride solution and dried with anhydrous sodium sulfate. After concentration under reduced pressure, the residue was purified by silica gel column chromatography (Isco Combiflash, 40 g, hexane:ethyl acetate=0:100 to 100:0, gradient) to obtain the title compound (24.6 g, 97%) as a black oily substance.

Workup

  1. extractionextracted with ethyl acetate
  2. washthe organic layer was washed with water
  3. dry with materiala 1 M aqueous hydrochloric acid solution, and saturated sodium chloride solution and dried with anhydrous sodium sulfate
  4. concentrationAfter concentration under reduced pressure
  5. customthe residue was purified by silica gel column chromatography (Isco Combiflash, 40 g, hexane:ethyl acetate=0:100 to 100:0, gradient)

Sources & evidence

ORD record
ord-385a33b9d93a4834b615ecaf46f3ea5f
Source dataset
uspto-grants-2015_01
Patent number
US08927536B2

Reaction notes

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