Piperazine → 1-(4-Methoxypyridin-2-yl)piperazine

HRID 270770

Reaction equation

HRID 270770 reaction equation
Cl[C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][N:3]=1.[NH:10]1[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1>CN(C)C=O>[CH3:9][O:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([N:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)[CH:7]=1

Participants

4

Reactant 2

HCID 4837PiperazineHCID 19911282-Chloro-4-methoxypyridine

Product 1

HCID 226481321-(4-Methoxypyridin-2-yl)piperazine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
115 °C

Procedure

To 756 mg (5.29 mmol) of 2-Chloro-4-methoxypyridine and 2.27 g (26 mmol) of piperazine in a pressure flask was added 2.7 mL dimethylformamide, and the mixture was heated at 115° C. for 5 hours. The solution was allowed to cool before opening the flask, and the resulting slurry was partitioned between ethyl acetate and water. The phases were separated, and the aqueous phase was back-extracted once with ethyl acetate. The combined ethyl acetate phases were washed once with brine, dried over Na2SO4, filtered, and the filtrate was acidified with 2M HCl in ether. The product crystallized over night, and the solids were isolated by filtration to yield product as a white solid: 1H NMR (D2O, 400 MHz) 7.72 (d, 1H), 6.61 (d, 1H), 6.48 (s, 1H), 3.88 (s, 3H), 3.79 (m, 4H), 3.36 (m, 4H) ppm.

Workup

  1. temperatureto cool
  2. customthe resulting slurry was partitioned between ethyl acetate and water
  3. customThe phases were separated
  4. extractionthe aqueous phase was back-extracted once with ethyl acetate
  5. washThe combined ethyl acetate phases were washed once with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customThe product crystallized over night
  9. customthe solids were isolated by filtration
  10. customto yield product as a white solid

Sources & evidence

ORD record
ord-7a4f4982e8e243fb84d125f179c1422b
Source dataset
uspto-grants-2008_11
Patent number
US07449576B1

Linked notes

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