Lithium Chloride → HCID 68465953, compound

HRID 506162Notes

Reaction equation

HRID 506162 reaction equation
[Cl:1][CH2:2][CH2:3][O:4][C:5]1[CH:6]=[C:7]([C:11]2[C:12](=O)[C:13]([C:28]#[N:29])=[CH:14][N:15](CC3C=CC(OC)=C(OC)C=3)[CH:16]=2)[CH:8]=[CH:9][CH:10]=1.[Li+].[Cl-:32]>O=P(Cl)(Cl)Cl>[Cl:32][C:12]1[C:13]([C:28]#[N:29])=[CH:14][N:15]=[CH:16][C:11]=1[C:7]1[CH:8]=[CH:9][CH:10]=[C:5]([O:4][CH2:3][CH2:2][Cl:1])[CH:6]=1

Participants

4

Reactant 2

HCID 433294Lithium ChlorideHCID 68466006HCID 68466006, compound

Product 1

HCID 68465953HCID 68465953, compoundYield 75.2%

Reagents, catalysts & solvents 1

HCID 24813Phosphorus oxychlorideSolvent

Procedure

A solution of 5-[3-(2-chloroethoxy)-phenyl]-1-(3,4-dimethoxybenzyl)-4-oxo-1,4-dihydro-pyridine-3-carbonitrile (2.5 g, 5.9 mmol) and LiCl (2.3 g, 53 mmol) in 22 mL of POCl3 was heated at reflux for 2.5 h. The excess POCl3 was removed by concentrating in vacuo. The residue was dissolved in 100 mL CH2Cl2 and washed with ice-cold 3 N NaOH. The organic layer was separated, dried over anhydrous MgSO4, filtered, concentrated in vacuo, and purified by flash chromatography on silica gel eluting with 30% EtOAc in hexanes to yield 1.3 g (75% yield) of 4-chloro-5-[3-(2-chloroethoxy)phenyl]nicotinonitrile as an off-white solid.

Workup

  1. temperatureat reflux for 2.5 h
  2. customThe excess POCl3 was removed
  3. concentrationby concentrating in vacuo
  4. dissolutionThe residue was dissolved in 100 mL CH2Cl2
  5. washwashed with ice-cold 3 N NaOH
  6. customThe organic layer was separated
  7. dry with materialdried over anhydrous MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. custompurified by flash chromatography on silica gel eluting with 30% EtOAc in hexanes

Sources & evidence

ORD record
ord-27ed6fea806f41ed80bddac16d27eaa3
Source dataset
uspto-grants-2010_08
Patent number
US07781591B2

Reaction notes

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