Hydrochloric Acid → 2-(4-Methoxyphenyl)-2-methylpropanenitrile

HRID 228164

Reaction equation

HRID 228164 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[K+].F[C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=1.[C:20](#[N:24])[CH:21]([CH3:23])[CH3:22].Cl>O1CCCC1>[CH3:19][O:18][C:15]1[CH:16]=[CH:17][C:12]([C:21]([CH3:23])([CH3:22])[C:20]#[N:24])=[CH:13][CH:14]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6559IsobutyronitrileHCID 99874-FluoroanisoleHCID 3251421Potassium bis(trimethylsilyl)amide

Product 1

HCID 2191662-(4-Methoxyphenyl)-2-methylpropanenitrileYield 52%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Add potassium bis(trimethylsilyl)amide (39.90 g, 200 mmol) to a stirred solution of 4-fluoroanisole (15.0 mL, 133 mmol), isobutyronitrile (49.0 mL, 539 mmol) and anhydrous tetrahydrofuran (150 mL). Heat the reaction to reflux under nitrogen for 72 h. Cool the reaction to room temperature, pour it into 1 N hydrochloric acid (300 mL), and extract with diethyl ether (3×100 mL). Wash the diethyl ether extracts with brine (100 mL), dry the extracts over magnesium sulfate, filter, and concentrate on a rotary evaporator to give the crude product. The crude product is purified by flash chromatography on silica gel eluting with 10% ethyl acetate/hexanes to yield 12.13 g (52%) of 2-(4-methoxy-phenyl)-2-methyl-propionitrile: TLC: Rf in 10% ethyl acetate/hexanes: 0.30; 1H NMR (CDCl3): 7.40-7.37 (m, 2H), 6.92-6.90 (m, 2H), 3.81 (s, 3H), 1.70 (s, 6H).

Workup

  1. temperatureHeat
  2. customthe reaction
  3. temperatureto reflux under nitrogen for 72 h
  4. temperatureCool
  5. customthe reaction to room temperature
  6. extractionextract with diethyl ether (3×100 mL)
  7. washWash the diethyl ether
  8. dry with materialdry the extracts over magnesium sulfate
  9. filtrationfilter
  10. concentrationconcentrate on a rotary evaporator
  11. customto give the crude product
  12. customThe crude product is purified by flash chromatography on silica gel eluting with 10% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-f3dcd6e3ee9947f6902923fb0c4cec45
Source dataset
uspto-grants-2009_07
Patent number
US07560463B2

Linked notes

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