Electric Literature of 4949-13-7,Some common heterocyclic compound, 4949-13-7, name is 2-Fluoropyrazine, molecular formula is C4H3FN2, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
n-Butyllithium (2.5M in hexanes, 1.05 mL, 2.58 mmol) was added to a solution of 2,2,6,6-tetramethylpiperidine (462 muL, 2.73 mmol) in THF (10 mL) at -78 C. The reaction mixture was stirred at 0 C. for 20 min. A solution of 2-fluoropyrazine (224 mg, 2.28 mmol) in THF was added at -78 C. After stirring at -78 C. for 5 min, ZnCl2 (0.5 M in THF, 11 mL, 5.32 mmol) was then added. The reaction mixture was stirred at -78 C. for 30 min and then at 0 C. for 1 h. A solution of the bromide (500 mg, 1.52 mmol) and Pd(PPh3)4 (352 mg, 0.304 mmol) in THF (20 mL) was then added. The reaction mixture was stirred at rt for 3 days. A sat. aq. solution of EDTA was added. After stirring at rt for 15 min, a sat. aq. solution of NaHCO3 was added. The reaction mixture was extracted with DCM. The combined organics were separated, dried (MgSO4), filtered and concentrated. The crude residue was purified by SiO2 chromatography eluting with 20:80 EtOAc/hexane to afford 200 mg (38%) of pyrazine as a yellow oil. MS m/z (ES): 346 (M+H)+.
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-Fluoropyrazine, its application will become more common.