Reaction #2260921

Reaction equation

2-chloro-3,5-dimethylpyrazine

sodium carbonate

4-(1-naphthyl)phenylboronic acid

→

3,5-Dimethyl-2-(4-naphthalen-1-yl-phenyl)pyrazine

Yield 50.0%

Solvents

Water

acetonitrile

water

Conditions

Workup

1. 1
   OtherFirst, into a recovery flask equipped with a reflux pipe
2. 2
   OtherThis reaction container was irradiated with microwaves (2.45 GHz, 100 W) for 15 minutes
3. 3
   Temperatureso that heating
4. 4
   TemperatureThen, the reaction container was cooled to 50° C. or less
5. 5
   Extractionthe organic layer was extracted with dichloromethane
6. 6
   WashThe obtained organic layer was washed with water
7. 7
   Dryingdried with magnesium sulfate
8. 8
   OtherThe solution which had been dried
9. 9
   Filtrationwas filtered
10. 10
    workup.DISTILLATIONThe solvent of this solution was distilled
11. 11
    Otherrecrystallized
12. 12
    Otherto be produced
13. 13
    Otherwas obtained (as a white powder in 50% yield)
14. 14
    OtherNote that the microwave irradiation
15. 15
    Othera microwave synthesis system (Discover, manufactured by CEM Corporation)
16. 16
    OtherThe synthesis scheme of Step 1

Procedure

First, into a recovery flask equipped with a reflux pipe were placed 0.74 g of 2-chloro-3,5-dimethylpyrazine, 1.29 g of 4-(1-naphthyl)phenylboronic acid, 0.55 g of sodium carbonate, 0.024 g of bis(triphenylphosphine)palladium(II)dichloride (abbreviation: Pd(PPh3)2Cl2), 10 mL of water, and 10 mL of acetonitrile, and the air in the flask was replaced with argon. This reaction container was irradiated with microwaves (2.45 GHz, 100 W) for 15 minutes, so that heating was performed. Then, the reaction container was cooled to 50° C. or less. Water was added to the reaction solution, and the organic layer was extracted with dichloromethane. The obtained organic layer was washed with water and dried with magnesium sulfate. The solution which had been dried was filtered. The solvent of this solution was distilled, and recrystallized using ethyl acetate, whereby Hdm1nppr, which is the pyrazine derivative to be produced, was obtained (as a white powder in 50% yield). Note that the microwave irradiation was performed using a microwave synthesis system (Discover, manufactured by CEM Corporation). The synthesis scheme of Step 1 is illustrated in the following (a-1).

Source