Potassium Carbonate → 3'-(Phenyl)-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-carboxylic acid t-butyl ester

HRID 220421Notes

Reaction equation

HRID 220421 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:19](Cl)=[N:18][CH:17]=[CH:16][N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:21]1(B(O)O)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C(=O)C.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:19]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[N:18][CH:17]=[CH:16][N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 11150691Tert-butyl 4-(3-chloropyrazin-2-yl)piperazine-1-carboxylate

Product 1

HCID 687380133'-(Phenyl)-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-carboxylic acid t-butyl esterYield 87.1%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Procedure

Dissolve 3′-chloro-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-carboxylic acid t-butyl ester (2.50 g, 8.40 mmol) and phenylboronic acid (1.23 g, 10.08 mmol) in N,N-dimethylacetamide (25 mL) and water (10 mL). Add tetrakis(triphenylphosphine) palladium(0) (0.49 g, 0.42 mmol) and potassium carbonate (2.80 g, 20.16 mmol). Heat for 4 hr. at 114° C. and allow to cool about 1.5 hr. to room temperature. Partition reaction mixture between MTBE and water. Separate layers. Dry organic layer (sodium sulfate), filter, concentrate and purify (silica gel chromatography eluting with 10:90 to 30:70 ethyl acetate:hexanes), to give 3′-(phenyl)-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-carboxylic acid t-butyl ester (2.49 g, 87%). MS (ES): m/z=341 [M+H]+.

Workup

  1. temperatureHeat for 4 hr
  2. customat 114° C.
  3. temperatureto cool about 1.5 hr
  4. customto room temperature
  5. customPartition
  6. customreaction mixture between MTBE and water
  7. filtrationDry organic layer (sodium sulfate), filter
  8. concentrationconcentrate
  9. custompurify
  10. wash(silica gel chromatography eluting with 10:90 to 30:70 ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-3238288fb8524cc39e6aed325413d9b0
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

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