Potassium Carbonate → HCID 67367110, compound

HRID 220417Notes

Reaction equation

HRID 220417 reaction equation
Cl[C:2]1[C:7](Cl)=[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+].[F:28][C:29]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=1>O.C(OC)(C)(C)C.CN(C)C(=O)C>[F:28][C:29]1[CH:34]=[CH:33][C:32]([C:2]2[C:7]([N:19]3[CH2:20][CH2:21][N:16]([C:14]([O:13][C:9]([CH3:12])([CH3:10])[CH3:11])=[O:15])[CH2:17][CH2:18]3)=[N:6][CH:5]=[CH:4][N:3]=2)=[CH:31][CH:30]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 785752,3-DichloropyrazineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 2856454-Fluorophenylboronic acid

Product 1

HCID 67367110HCID 67367110, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 15413tert-Butyl methyl etherSolventHCID 31374DimethylacetamideSolvent

Procedure

Charge a reactor with 2,3-dichloropyrazine (73.6 g, 0.497 mol, 1.0 equiv), piperazine-1-carboxylic acid t-butyl ester (101.9 g, 0.547 mol, 1.1 equiv) and powdered potassium carbonate (164.8 g, 1.19 mol, 2.4 equiv). Add N,N-dimethylacetamide (1.1 L) and heat to 110° C. under nitrogen for 5 hr. Cool the reaction to room temperature, and add 4-fluorophenylboronic acid (83.4 g, 0.596 mol, 1.2 equiv), tetrakis(triphenyl-phosphine)palladium(0) (2.87 g, 2.5 mmol, 0.005 equiv) and water (442 mL). Heat the reaction to 110° C. under a nitrogen atmosphere for 5 hr. Cool the reaction to 60° C. and dilute with water (800 mL) and methyl t-butyl ether (1.0 L). Cool to room temperature and separate the resulting layers. Wash the organic layer with 200 mL of water, separate the layers, and concentrate to give 3-(4-fluorophenyl)-2-[4-(t-butyloxycarbonyl)piperazin-1-yl]pyrazine as a light yellow solid that is taken into the next step without further purification.

Workup

  1. temperatureCool
  2. customthe reaction to room temperature
  3. temperatureHeat
  4. customthe reaction to 110° C. under a nitrogen atmosphere for 5 hr
  5. temperatureCool
  6. customthe reaction to 60° C.
  7. customseparate the resulting layers
  8. washWash the organic layer with 200 mL of water
  9. customseparate the layers
  10. concentrationconcentrate

Sources & evidence

ORD record
ord-bfab73f964b345669c17b7b1453986c5
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

Loading…