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

HRID 220418Notes

Reaction equation

HRID 220418 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].[CH3:21][C:22]1[CH:23]=[C:24](B(O)O)[CH:25]=[CH:26][CH:27]=1.C(=O)([O-])[O-].[K+].[K+]>C(COC)OC.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:26]3[CH:27]=[C:22]([CH3:21])[CH:23]=[CH:24][CH:25]=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 27339503-Tolylboronic acidHCID 11150691Tert-butyl 4-(3-chloropyrazin-2-yl)piperazine-1-carboxylate

Product 1

HCID 687368123'-m-Tolyl-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-carboxylic acid t-butyl esterYield 47%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

Dissolve 3′-chloro-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-carboxylic acid t-butyl ester (6.0 g, 20.2 mmol) and 3-methylbenzeneboronic acid (3.3 g, 24.0 mmol) in dimethoxyethane (20 mL) and water (10 mL). Add tetrakis(triphenylphosphine) palladium(0) (2.3 g, 2.0 mmol) and potassium carbonate (7.5 g, 54 mmol). Heat for 17 hr. at 102° C. and allow to cool about 1.5 hr. to room temperature. Partition reaction mixture between ethyl acetate and water. Separate layers. Wash organic layer with brine, dry (sodium sulfate), filter, concentrate and purify (silica gel chromatography eluting with 10:90 to 20:80 ethyl acetate:hexanes), to give 3′-m-tolyl-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-carboxylic acid t-butyl ester (3.3 g, 47%). MS (ES): m/z=355 [M+H]+.

Workup

  1. temperatureHeat for 17 hr
  2. customat 102° C.
  3. temperatureto cool about 1.5 hr
  4. customto room temperature
  5. customPartition
  6. customreaction mixture between ethyl acetate and water
  7. dry with materialWash organic layer with brine, dry (sodium sulfate)
  8. filtrationfilter
  9. concentrationconcentrate
  10. custompurify
  11. wash(silica gel chromatography eluting with 10:90 to 20:80 ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-67c6e63518c046a48b58480b6132fa8a
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

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