Methanol → (4-Bromo-2-methoxyphenyl)acetonitrile

HRID 338505Notes

Reaction equation

HRID 338505 reaction equation
CC(C)([O-])C.[K+].C1(C)C=CC(S([CH2:16][N+:17]#[C-])(=O)=O)=CC=1.[Br:20][C:21]1[CH:28]=[CH:27][C:24]([CH:25]=O)=[C:23]([O:29][CH3:30])[CH:22]=1.CO>COCCOC>[Br:20][C:21]1[CH:28]=[CH:27][C:24]([CH2:25][C:16]#[N:17])=[C:23]([O:29][CH3:30])[CH:22]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 161915Tosylmethyl isocyanideHCID 110530414-Bromo-2-methoxybenzaldehydeHCID 23665647Potassium tert-butoxide

Product 1

HCID 52987748(4-Bromo-2-methoxyphenyl)acetonitrileYield 82.4%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent2×

Procedure

To a solution of potassium tert-butoxide (6.5 g, 0.058 mol) in 1,2-dimethoxyethane (150 mL) was added p-toluenesulfonylmethyl isocyanide (5.6 g, 0.029 mol) portionwise at −78° C. Then a solution of 4-bromo-2-methoxybenzaldehyde (6.3 g, 0.029 mol) in 1,2-dimethoxyethane was added dropwise and the reaction mixture was warmed to room temperature. The mixture was stirred at room temperature for 1 hour and methanol (150 mL) was added, then heated to reflux and stirred for 2 hours. Solvent was evaporated, and saturated ammonium chloride (100 mL) was added and extracted with ethyl acetate (100 mL×2). The organic layers were combined, dried over sodium sulfate and concentrated in vacuo to give a residue, which was purified by combiflash (Petroleum ether/EtOAc=10:1 to 5:1) to give the title compound (5.4 g, 82%) as a light yellow solid.

Workup

  1. temperatureheated
  2. temperatureto reflux
  3. stirringstirred for 2 hours
  4. customSolvent was evaporated
  5. additionsaturated ammonium chloride (100 mL) was added
  6. extractionextracted with ethyl acetate (100 mL×2)
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customto give a residue, which
  10. customwas purified by combiflash (Petroleum ether/EtOAc=10:1 to 5:1)

Sources & evidence

ORD record
ord-a85f2c6740044f6db6c399157b664ce9
Source dataset
uspto-grants-2014_11
Patent number
US08889730B2

Reaction notes

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