Some common heterocyclic compound, 1174321-06-2, name is 5-(Difluoromethyl)pyrazine-2-carboxylic acid, molecular formula is C6H4F2N2O2, 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. category: Pyrazines
5-(Difluoromethyl)pyrazine-2-carboxylic acid 42 (0.68 wt, 1.1 eq) was charged into a reactor and if needed, dried by azeotropic distillation with toluene. DMI (2.0V) was added and the mixture was cooled down to 0-5 C. Thionyl chloride (0.337 V, 1.30 eq) was added while keeping the internal T below 10 C. The resulting solution was stirred at 4-10 C until the conversion was >95.0 % by HPLC. The mixture was cooled down to 0 C and a solution of 39 (1.0 Wt, 1.0 eq) in DMI (2.5V) was charged while keeping the internal temperature below 5 C. The vessel was rinsed with DMI (0.50V) and the reaction mixture was stirred until the conversion is >99%. Water (12V) was charged and the resulting mixture is stirred at 15-20 C for 0.5h. EtOAc (15V) and then 50% aq. NaOH (1.5 Wt, 5.3 eq) were added while keeping T below 30 C. pH was monitored to make sure that it is above 10. The aqueous phase was separated and extracted with EtOAc (5.0V). Theorganic layers were combined and washed with brine (5.0V) and water twice (5.0V each). The mixture was filtered through a Celite pad (0.50 Wt) rinsing with EtOAc (3.0V). The filtrate was concentrated under reduced pressure at 40-50 C. 1-Propanol (15V) was charged and the mixture was warmed up to 90-100 C while stirring until a clear solution was obtained. The mixture was cooled down to 0-5 C over 2h and stired over lh. The mixture was filtered, rinsing with cold 1-propanol twice (2.5V each). Drying in an oven vacuum at 45 C overnight provided the title compound 43 as an off-white solid in 81% isolated yield.
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1174321-06-2, its application will become more common.
Reference:
Patent; ???????????????????????????; ? Buranko; Kimu ?; Chan ?; ?; Yoshizawa Kazuhiro; (94 pag.)JP2016/121177; (2016); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem