1,4-Dioxane hydrochloride → Ethyl 5-chloro-6-(piperazin-1-YL)nicotinate

HRID 1444100Notes

Reaction equation

HRID 1444100 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:19]([Cl:20])=[CH:18][C:17]([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:16][N:15]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.Cl.O1CCOCC1>O1CCOCC1>[CH2:24]([O:23][C:21](=[O:22])[C:17]1[CH:18]=[C:19]([Cl:20])[C:14]([N:11]2[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]2)=[N:15][CH:16]=1)[CH3:25]

Participants

4

Reactant 2

HCID 204431481,4-Dioxane hydrochloride2×HCID 59168365Ethyl 6-[1-(tert-butoxycarbonyl)piperazin-4-yl]-5-chloronicotinate

Product 1

HCID 22028944Ethyl 5-chloro-6-(piperazin-1-YL)nicotinate

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

Dissolve a solution of 4-(3-chloro-5-ethoxycarbonyl-pyridin-2-yl)piperazine-1-carboxylic acid tert-butyl ester (7.78 g, 0.021 mol) in dioxane, and then add a solution of 4M HCl/dioxane (12 mL). Stir at 50° C. for 2 h, and then add additional 4M HCl/dioxane (5 mL) and stir for an additional 1 h. Cool the mixture in ice, collect the precipitate and wash with ether. Prepare the freebase by partitioning between EtOAc and 10% NaOH solution. Dry the organic layer (Na2SO4) and concentrate under reduced pressure to give the title compound.

Workup

  1. stirringstir for an additional 1 h
  2. temperatureCool the mixture in ice
  3. customcollect the precipitate
  4. washwash with ether
  5. customPrepare the freebase
  6. customby partitioning between EtOAc and 10% NaOH solution
  7. dry with materialDry the organic layer (Na2SO4)
  8. concentrationconcentrate under reduced pressure

Sources & evidence

ORD record
ord-dfb29871171e443c921a6204d3e55efd
Source dataset
uspto-grants-2010_02
Patent number
US07662830B2

Reaction notes

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