Ethyl formate → 3,5-Dichloropyrazine-2-carbaldehyde

To THF (200 mL) at −30° C. under N2 is added n-butyllithium (2.5 M in hexane, 8 mL, 20 mmol), followed by 2,2,6,6-tetramethylpiperidine (3.5 mL, 20.5 mmol). The mixture is warmed to room temperature and stirred at this temperature for 10 minutes. After the mixture is cooled to −78° C., 2,6-dichloropyrazine (2.5 g, 16.75 mmol) in THF (25 mL) is added and the mixture is stirred at this temperature for 1 hour. To the mixture is added ethyl formate (2 mL, 24.4 mmol) and the mixture is stirred at this temperature for an additional 2 hours. The reaction is quenched with saturated NH4Cl (25 mL), warmed to room temperature, and diluted with ethyl acetate (200 mL). The organic layer is separated and dried, and solvent removed. Column chromatography on silica gel (15% ethyl acetate in hexane) gives 2.4 g of 3,5-dichloro-pyrazine-2-carbaldehyde as an oil.

1. temperatureAfter the mixture is cooled to −78° C.
2. stirringthe mixture is stirred at this temperature for 1 hour
3. stirringthe mixture is stirred at this temperature for an additional 2 hours
4. customThe reaction is quenched with saturated NH4Cl (25 mL)
5. temperaturewarmed to room temperature
6. additiondiluted with ethyl acetate (200 mL)
7. customThe organic layer is separated
8. customdried
9. customsolvent removed

ORD record

ord-c783996d71a0441da82815077e4210db

Source dataset

uspto-grants-2006_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06982268B2