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

HRID 553475Notes

Reaction equation

HRID 553475 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+].CN(C)C(=O)C>COC(C)(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 N,N-dimethylacetamide (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 t-butyl methyl ether (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-8eb413f6487544d89319f33e171954e1
Source dataset
uspto-grants-2011_11
Patent number
US08048884B2

Reaction notes

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