Ethylene Glycol → 4-Chloro-2-(2-hydroxy-ethoxy)benzonitrile

HRID 555715Notes

Reaction equation

HRID 555715 reaction equation
[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4](F)[CH:3]=1.[CH2:11]([OH:14])[CH2:12][OH:13].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([O:13][CH2:12][CH2:11][OH:14])[CH:3]=1

Participants

5

Reactant 3

HCID 174Ethylene GlycolHCID 11430Potassium CarbonateHCID 936554-Chloro-2-fluorobenzonitrile

Product 1

HCID 630935884-Chloro-2-(2-hydroxy-ethoxy)benzonitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 4-chloro-2-fluoro-benzonitrile (1.00 g, 6.43 mmol), ethylene glycol (3.59 mL, 64.3 mmol) and K2CO3 (1.33 g, 9.64 mmol) in DMF (30 mL) is stirred at RT for 12 h. The reaction mixture is quenched by H2O. EtOAc is added and the organic layer is washed with brine, dried over MgSO4. Concentration in vacuo affords the corresponding 4-chloro-2-(2-hydroxy-ethoxy)-benzonitrile. A THF (6 mL) solution of 4-chloro-2-(2-hydroxy-ethoxy)benzonitrile (875 mg, 4.43 mmol) is added to a suspension of LAH (504 mg, 13.2 mmol) in THF (45 mL) at 0° C. The reaction is allowed to stir for 2 h at ambient temperature and then quenched by Na2SO4.10H2O, and the product is isolated by filtration with Celite and washed with THF and dried under reduced pressure to give the title compound as colorless solid; ES-MS: M+=202.1; HPLC: AtRet=1.90 min

Workup

  1. customThe reaction mixture is quenched by H2O
  2. additionEtOAc is added
  3. washthe organic layer is washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationConcentration in vacuo

Sources & evidence

ORD record
ord-e7cd029bc90249098f0295da9a21f7a2
Source dataset
uspto-grants-2011_11
Patent number
US08053457B2

Reaction notes

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