Piperazine → 1-(3-Methoxypyridin-2-yl)piperazine

HRID 1371991Notes

Reaction equation

HRID 1371991 reaction equation
Cl[C:2]1[CH:7]=[CH:6][CH:5]=[C:4](OC)[N:3]=1.[NH:10]1[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1.CN(C)[CH:18]=[O:19]>>[CH3:18][O:19][C:5]1[C:4]([N:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[N:3][CH:2]=[CH:7][CH:6]=1

Participants

4

Reactant 3

HCID 4837PiperazineHCID 6228DimethylformamideHCID 870092-Chloro-6-methoxypyridine

Product 1

HCID 127904951-(3-Methoxypyridin-2-yl)piperazine

Conditions

Temperature
115 °C

Procedure

To 966 mg (6.7 mmol) of 2-Chloro-6-methoxypyridine and 2.90 g (34 mmol) of piperazine in a pressure flask was added 3.3 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 overnight, and was isolated by filtration to give a white solid: 1H NMR (D2O, 400 MHz) 7.73 (t, 1H), 6.52 (d, 1H), 6.31 (d, 1H), 3.81 (s, 3H), 3.68 (m, 4H), 3.26 (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 overnight
  9. customwas isolated by filtration
  10. customto give a white solid

Sources & evidence

ORD record
ord-a4851646bba24a05b405ac5c86e55c85
Source dataset
uspto-grants-2007_01
Patent number
US07157464B2

Reaction notes

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