Potassium Carbonate → Tert-butyl 4-(3-chloropyrazin-2-yl)piperazine-1-carboxylate

HRID 220416Notes

Reaction equation

HRID 220416 reaction equation
Cl[C:2]1[C:7]([Cl:8])=[N:6][CH:5]=[CH:4][N:3]=1.[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10].C(=O)([O-])[O-].[K+].[K+].CC(N(C)C)=O>CC(OC)(C)C.O>[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][N:19]([C:2]2[C:7]([Cl:8])=[N:6][CH:5]=[CH:4][N:3]=2)[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:10])[CH3:11]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 31374DimethylacetamideHCID 785752,3-DichloropyrazineHCID 143452tert-Butyl piperazine-1-carboxylate

Product 1

HCID 11150691Tert-butyl 4-(3-chloropyrazin-2-yl)piperazine-1-carboxylateYield 91.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
110 °C

Procedure

Charge a 2 L 3-neck round bottom flask with 2,3-dichloropyrazine (78.7 g, 0.532 mol), piperazine-1-carboxylic acid t-butyl ester (100 g, 0.537 mol), potassium carbonate (88.2 g, 0.638 mol) followed by DMA (0.780 L), and heat the resultant slurry to 110° C. under nitrogen with vigorous stirring. Cool to room temperature, add water (0.390 L) and MTBE (0.390 L), and stir the mixture for 60 min. Stop stirring and separate the layers. Wash the organic layer with water (2×200 mL), dry over MgSO4, filter and concentrate to give the title preparation as a yellow syrup (145 g, 91% yield).

Workup

  1. temperatureCool to room temperature
  2. stirringStop stirring
  3. customseparate the layers
  4. washWash the organic layer with water (2×200 mL)
  5. dry with materialdry over MgSO4
  6. filtrationfilter
  7. concentrationconcentrate
  8. customto give the title

Sources & evidence

ORD record
ord-251aa1af9b044810b592aa9a93592f08
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

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