Reaction #1891186

Reaction equation

2-chloro-3,5-dimethylpyrazine

1-Boc-piperazine

2-(dicyclohexylphosphino)-2′,4′,6′-tri-isopropyl-1,1′-biphenyl

sodium tert-butoxide

→

3′,5′-dimethyl-2,3,5,6-tetrahydro[1,2′]bipyrazinyl-4-carboxylic acid tert-butyl ester

Yield 87.1%

Solvents

toluene

Conditions

Workup

1. 1
   Temperaturethe mixture was refluxed for 8 hr
2. 2
   TemperatureAfter cooling
3. 3
   Extractionthe mixture was extracted with ethyl acetate
4. 4
   WashThe organic layer was washed with saturated brine
5. 5
   Otherthe solvent was evaporated
6. 6
   OtherThe residue was purified by column chromatography (hexane:ethyl acetate)

Procedure

To a mixture of 2-chloro-3,5-dimethylpyrazine (2.8 g), 1-Boc-piperazine (3.7 g), palladium (II) acetate (225 mg), 2-(dicyclohexylphosphino)-2′,4′,6′-tri-isopropyl-1,1′-biphenyl (953 mg) and sodium tert-butoxide (2.7 g) was added toluene (40 mL), and the mixture was refluxed for 8 hr. After cooling, the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and the solvent was evaporated. The residue was purified by column chromatography (hexane:ethyl acetate) to give 3′,5′-dimethyl-2,3,5,6-tetrahydro[1,2′]bipyrazinyl-4-carboxylic acid tert-butyl ester (5 g). 3′,5′-Dimethyl-2,3,5,6-tetrahydro[1,2′]bipyrazinyl-4-carboxylic acid tert-butyl ester (5 g) was dissolved in chloroform (15 mL), 4N hydrogen chloride/ethyl acetate (15 mL) was added, and the mixture was stirred at room temperature overnight. Ethyl acetate (100 mL) was added, and the mixture was filtered to give the title compound (3.3 g).

Source