N-Methoxy-N-methylacetamide → 2-(4-Acetyl-2-methylphenyl)-2-methylpropanenitrile

HRID 419963Notes

Reaction equation

HRID 419963 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH3:12])([CH3:11])[C:9]#[N:10])=[C:4]([CH3:13])[CH:3]=1.C([Li])CCC.CON(C)[C:22](=[O:24])[CH3:23]>C1COCC1.[Cl-].[Na+].O>[C:22]([C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH3:12])([CH3:11])[C:9]#[N:10])=[C:4]([CH3:13])[CH:3]=1)(=[O:24])[CH3:23]

Participants

6

Reactant 3

HCID 537505N-Methoxy-N-methylacetamideHCID 582984672-(4-Bromo-2-methylphenyl)-2-methylpropanenitrileHCID 178418339Butyllithium

Product 1

HCID 582984812-(4-Acetyl-2-methylphenyl)-2-methylpropanenitrileYield 68%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a stirred solution of 2-(4-bromo-2-methylphenyl)-2-methylpropanenitrile (3.1 g, 13.0 mmol) in anhydrous THF (75 mL) at −78° C. is added n-butyllithium (2 M in c-hexane) (7.16 mL, 14.3 mmol). This reaction mixture is stirred at that temperature 10 min., then N-methoxy-N-methyl-acetamide (2.77 mL, 26.0 mmol) is added and the solution is then warmed up to room temperature over 1 h. Acidic brine (30 mL of brine, 15 mL of 3% HCl aq) is then slowly added and the solution extracted with EtOAc (3×100 mL). The organic layer is dried with MgSO4, filtered and concentrated under reduced pressure. The crude product is purified by flash-chromatography using a 5 to 20% EtOAc in hexane gradient to provide the expected product 2-(4-acetyl-2-methylphenyl)-2-methylpropanenitrile (1.77 g, 68%) as a yellowish oil. 1H NMR (300 MHz, CHLOROFORM-D): δ 7.84-7.74 (2H, m), 7.43-7.40 (1H, m), 2.70 (3H, s), 2.60 (3H, s), 1.81 (6H, s).

Workup

  1. extractionthe solution extracted with EtOAc (3×100 mL)
  2. dry with materialThe organic layer is dried with MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe crude product is purified by flash-chromatography

Sources & evidence

ORD record
ord-9931a6a5529d4ee7a39378679d178d3c
Source dataset
uspto-grants-2012_01
Patent number
US08093402B2

Reaction notes

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