Sodium Iodide → 1-(4-chlorobenzyl)-5-(4-fluorophenoxy)pyridin-2(1H)-one

HRID 1948274Notes

Reaction equation

HRID 1948274 reaction equation
[F:1][C:2]1[CH:16]=[CH:15][C:5]([O:6][C:7]2[CH:8]=[CH:9][C:10]([O:13]C)=[N:11][CH:12]=2)=[CH:4][CH:3]=1.[Cl:17][C:18]1[CH:25]=[CH:24][C:21]([CH2:22]Cl)=[CH:20][CH:19]=1.[Na+].[I-]>C(#N)C>[Cl:17][C:18]1[CH:25]=[CH:24][C:21]([CH2:22][N:11]2[CH:12]=[C:7]([O:6][C:5]3[CH:15]=[CH:16][C:2]([F:1])=[CH:3][CH:4]=3)[CH:8]=[CH:9][C:10]2=[O:13])=[CH:20][CH:19]=1

Participants

5

Reactant 3

HCID 5238Sodium IodideHCID 77231-Chloro-4-(chloromethyl)benzeneHCID 442541925-(4-Fluorophenoxy)-2-methoxypyridine

Product 1

HCID 589669211-(4-chlorobenzyl)-5-(4-fluorophenoxy)pyridin-2(1H)-oneYield 27%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

According to Scheme 32 Step 1: 5-(4-Fluorophenoxy)-2-methoxypyridine (2.37 mmol, 520 mg), 4-chlorobenzylchloride (3.55 mmol, 603 mg), NaI (2.37 mmol, 356 mg) in acetonitrile (15 mL) was heated at 150° C. for 20 minutes under microwave conditions. The cooled crude reaction washed with water, extracted with AcOEt. The organic layer was collected, dried (Na2SO4) and the solvent was evaporated under reduced pressure. The residue was purified in a manifold (vac.) using a Sep-Pak silica cartridge (heptane/AcOEt, 90:10 to CH2Cl2) and then CH2Cl2/acetone 90:10), following HPLC purification yielding 1-(4-chlorobenzyl)-5-(4-fluorophenoxy)pyridin-2(1H)-one (211 mg, 27%).

Workup

  1. temperatureThe cooled crude
  2. customreaction
  3. washwashed with water
  4. extractionextracted with AcOEt
  5. customThe organic layer was collected
  6. dry with materialdried (Na2SO4)
  7. customthe solvent was evaporated under reduced pressure
  8. customThe residue was purified in a manifold (vac.)
  9. customHPLC purification

Sources & evidence

ORD record
ord-8be4dd2a51f44dc6a36bff4fdc097106
Source dataset
uspto-grants-2013_03
Patent number
US08399493B2

Reaction notes

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