Hydrochloric Acid → 2-(4-Chloro-3-methoxyphenyl)-2-methylpropanenitrile

HRID 61799

Reaction equation

HRID 61799 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5](F)=[CH:4][C:3]=1[O:9][CH3:10].[C:11](#[N:15])[CH:12]([CH3:14])[CH3:13].C[Si]([N-][Si](C)(C)C)(C)C.[K+].Cl>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:12]([CH3:14])([CH3:13])[C:11]#[N:15])=[CH:4][C:3]=1[O:9][CH3:10]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6559IsobutyronitrileHCID 27245202-Chloro-5-fluoroanisoleHCID 3251421Potassium bis(trimethylsilyl)amide

Product 1

HCID 179891552-(4-Chloro-3-methoxyphenyl)-2-methylpropanenitrileYield 31%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
65 °C

Procedure

1-Chloro-4-fluoro-2-methoxy-benzene (4.3 g, 26.78 mmol) and isobutyronitrile (9.61 mL, 4.0 eq.) were dissolved in toluene (9.0 mL), added with KHMDS (80 mL, 0.5 M toluene solution) and stirred at 65° C. for 2 hr. The reaction solution was cooled to room temperature, added with aqueous solution of 1 N hydrochloric acid and then extracted with MTBE. The organic layer was washed with saturated brine and dried over magnesium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (hexane/ethyl acetate) to obtain the title compound (1.72 g, 31%).

Workup

  1. temperatureThe reaction solution was cooled to room temperature
  2. extractionextracted with MTBE
  3. washThe organic layer was washed with saturated brine
  4. dry with materialdried over magnesium sulfate
  5. customThe drying agent was removed by filtration
  6. customthe residues obtained
  7. concentrationafter concentration under reduced pressure
  8. customwere purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-1515b36c859648d1a5dd4503c6364978
Source dataset
uspto-grants-2016_09
Patent number
US09440922B2

Linked notes

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