N,N-Dimethylglycine → 5-(4-Fluorophenoxy)-2-methoxypyridine

HRID 1948273

Reaction equation

HRID 1948273 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([O:8][CH3:9])=[N:6][CH:7]=1.[F:10][C:11]1[CH:18]=[CH:17][C:14](CO)=[CH:13][CH:12]=1.CN(CC(O)=[O:24])C>O1CCOCC1.CN(C=O)C.[Cu]I>[F:10][C:11]1[CH:18]=[CH:17][C:14]([O:24][C:2]2[CH:3]=[CH:4][C:5]([O:8][CH3:9])=[N:6][CH:7]=2)=[CH:13][CH:12]=1

Participants

7

Reactant 3

HCID 673N,N-DimethylglycineHCID 680224-Fluorobenzylic alcoholHCID 27348955-Bromo-2-methoxypyridine

Product 1

HCID 442541925-(4-Fluorophenoxy)-2-methoxypyridine

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Procedure

According to Scheme 32 Method A: 5-Bromo-2-methoxypyridine (5.32 mmol, 1.00 g), 4-fluorobenzylalcohol (7.98 mmol, 0.90 g), N,N-dimethylaminoacetic acid (15.9 mmol, 1.69 g), CuI (5.32 mmol, 1.01 g), CsCO3 (12.4 mmol, 4.05 g) in dioxane (25 mL) and DMF (2.5 mL) were heated at 150° C. for 25 min. under microwave irradiation conditions. Then the cooled crude reaction was filtered off over celite. The filtrate was washed with saturated aqueous NH4Cl solution and extracted with AcOEt. The organic layer was separated, 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, 80/20). The product fractions were collected and the solvent was evaporated to give a mixture of the desired product contaminated with 4-fluorobenzylalcohol. This residue was taken up in AcOEt and washed with aqueous solution of NaOH 1N. The organic layer was separated, dried (Na2SO4) and the solvent was evaporated under reduced pressure giving 5-(4-fluorophenoxy)-2-methoxypyridine (520 mg, 45%).

Workup

  1. temperatureThen the cooled crude
  2. customreaction
  3. filtrationwas filtered off over celite
  4. washThe filtrate was washed with saturated aqueous NH4Cl solution
  5. extractionextracted with AcOEt
  6. customThe organic layer was separated
  7. dry with materialdried (Na2SO4)
  8. customthe solvent was evaporated under reduced pressure
  9. customThe residue was purified in a manifold (vac.)
  10. customThe product fractions were collected
  11. customthe solvent was evaporated
  12. customto give

Sources & evidence

ORD record
ord-4dc56a6c36af44608627fc4010fe7b5a
Source dataset
uspto-grants-2013_03
Patent number
US08399493B2

Linked notes

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