Toluene → Acetonitrile

HRID 1250312Notes

Reaction equation

HRID 1250312 reaction equation
Cl[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][CH3:10])=[C:5]([O:11][CH:12]2[CH2:16][CH2:15][CH2:14][CH2:13]2)[CH:4]=1.[C:17]1([CH3:23])C=CC=CC=1.[C-:24]#[N:25].[Na+].C(Cl)C1C=CC=CC=1>CN(C=O)C.COC(C)(C)C>[C:24]([CH2:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][CH3:10])=[C:5]([O:11][CH:12]2[CH2:16][CH2:15][CH2:14][CH2:13]2)[CH:4]=1)#[N:25].[C:17](#[N:25])[CH3:23]

Participants

8

Reactant 4

HCID 1140TolueneHCID 7503Benzyl ChlorideHCID 8929Sodium CyanideHCID 109007664-(Chloromethyl)-2-(cyclopentyloxy)-1-methoxybenzene

Product 2

HCID 6342AcetonitrileYield 92.2%HCID 107282283-(Cyclopentyloxy)-4-methoxyphenylacetonitrile

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
55 °C

Procedure

A 12 liter round bottom flask equipped with an overhead stirrer, and a distillation apparatus was flushed with nitrogen. The flask was charged with 4-chloromethyl-2-cyclopentyloxy-1-methoxybenzene (519 g, 2.15 mol, 1.0 equivalents) in a solution of toluene and t-butyl methyl ether. The reaction was concentrated under reduce pressure to a residue. To the 12 liter flask was charged DMF (1.44 kg) and sodium cyanide (142 g, 2.9 mol, 1.35 equivalents). The reaction was heated to 55° C. for 6 hours or until deemed complete by the disappearance of the benzyl chloride. The reaction was concentrated under reduced pressure to a residue. To the flask was charged t-butyl methyl ether (2.30 kg) and deionized water (800 mL). The contents of the flask were vigorously stirred, and allowed to settle. The top organic layer was isolated, washed three times with deionized water (3×800 mL), and concentrated under atmospheric pressure to a residue. To the flask was added acetonitrile (1.26 kg) and the distillation was continued until an additional 400 mL of solvent was collected. The product, 4-cyanomethyl-2-cyclopentyloxy-1-methoxybenzene, was isolated as a solution in acetonitrile (92.2% yield). This was used directly in the next step.

Workup

  1. customA 12 liter round bottom flask equipped with an overhead stirrer
  2. customa distillation apparatus was flushed with nitrogen
  3. concentrationThe reaction was concentrated
  4. concentrationThe reaction was concentrated under reduced pressure to a residue
  5. additionTo the flask was charged t-butyl methyl ether (2.30 kg) and deionized water (800 mL)
  6. customThe top organic layer was isolated
  7. washwashed three times with deionized water (3×800 mL)
  8. concentrationconcentrated under atmospheric pressure to a residue
  9. additionTo the flask was added acetonitrile (1.26 kg)
  10. distillationthe distillation
  11. customwas collected

Sources & evidence

ORD record
ord-5875bf293b0a43759e9a0dffaa5760d1
Source dataset
uspto-grants-2002_01
Patent number
US06337408B1

Reaction notes

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