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

HRID 419957Notes

Reaction equation

HRID 419957 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH3:12])([CH3:11])[C:9]#[N:10])=[CH:4][C:3]=1[CH3:13].[CH2:14]([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])=[CH:4][C:3]=1[CH3:13])(=[O:24])[CH3:23].[C:22]([C:2]1[CH:3]=[CH:4][C:5]([C:8]([CH3:11])([CH3:12])[C:9]#[N:10])=[C:6]([CH3:14])[CH:7]=1)(=[O:24])[CH3:23]

Participants

7

Reactant 3

HCID 537505N-Methoxy-N-methylacetamideHCID 582984722-(4-Bromo-3-methylphenyl)-2-methylpropanenitrileHCID 178418339Butyllithium

Product 2

HCID 582984812-(4-Acetyl-2-methylphenyl)-2-methylpropanenitrileYield 47.3%HCID 582984882-(4-Acetyl-3-methylphenyl)-2-methylpropanenitrile

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a stirred solution of 2-(4-bromo-3-methylphenyl)-2-methylpropanenitrile (5.0 g, 21.0 mmol) in anhydrous THF (75 mL) at −100° C. is added n-butyllithium (2 M in c-hexane) (21 mL, 42 mmol). This reaction mixture is stirred at that temperature 5 min., then N-methoxy-N-methyl-acetamide (4.33 g, 42 mmol) is added. 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 is extracted with EtOAc (3×100 mL). The organic layer is dried over MgSO4, filtered and concentrated under reduced pressure. The crude product is purified on silica gel using a 0 to 30% gradient of EtOAc in heptane to provide the expected product 2-(4-acetyl-2-methylphenyl)-2-methylpropanenitrile (1.0 g, 24%). 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 1.71 (s, 6 H) 2.53 (s, 3H) 2.56 (s, 3H) 7.30-7.38 (m, 2H) 7.70 (d, J=8.01 Hz, 1H)

Workup

  1. extractionthe solution is extracted with EtOAc (3×100 mL)
  2. dry with materialThe organic layer is dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe crude product is purified on silica gel using a 0 to 30% gradient of EtOAc in heptane

Sources & evidence

ORD record
ord-6399002d3cde4f55afbb8d3053c71113
Source dataset
uspto-grants-2012_01
Patent number
US08093402B2

Reaction notes

Loading…