Synthetic Route of 399-94-0,Some common heterocyclic compound, 399-94-0, name is 1-Bromo-2,5-difluorobenzene, molecular formula is C6H3BrF2, 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.
Step B: tert-Butyl [1-(2,5-difluorophenyl)-1-oxopent-4-yn-2-yl]carbamate An inerted vessel was charged dichloromethane (866 kg) and cooled to -20 to -10 C. Then iso-propylmagnesium chloride solution in THF (2M, 326.1 kg, 669 mol) was slowly added followed by 1-bromo-2,5-difluorobenzene (120.1 kg, 622 mol). After 2 h at this temperature, an additional charge of iso-propylmagnesium chloride in THF solution was slowly added (2M, 58.65 kg, 121 mol) and the reaction aged 1 h. Then, a drop-wise addition of a dichloromethane solution of tert-butyl (1-[methoxy(methyl)amino]-1-oxopent-4-yn-2-yl)carbamate (70.8 kg, 276 mol in 292 kg dichloromethane) was conducted over 2 h at -20 to -20 C. The mixture was then warmed to room temperature and stirred for 10 h. The reaction was then slowly reverse quenched into aqueous ammonium chloride (175.6 kg in 1550 kg of water) at 5-10 C. The solution pH was then adjusted to ?7 by adding 68 kg of con. HCl. The layers were then separated and the aqueous extracted with dichloromethane (414 kg). The combined organics were then dried with Na2SO4, filtered, treated with activated carbon (10 kg), filtered, and concentrated to 71-141 L. A constant volume (71-141 L) vacuum distillation solvent switch to n-heptane was then performed to crystallize the product. The slurry was then cooled to 0 C. and stirred 2 h. The slurry was filtered and the cake washed with n-heptane, 2-propanol, and then water. The solids were dried under vacuum at 40-50 C. overnight to give tert-butyl [1-(2,5-difluorophenyl)-1-oxopent-4-yn-2-yl]carbamate.
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1-Bromo-2,5-difluorobenzene, its application will become more common.
Reference:
Patent; Merck Sharp & Dohme Corp; Merck Sharp & Dohme Ltd.; Arroyo, Itzia Z.; Krueger, Davida; Chen, Ping; Moment, Aaron J.; Biftu, Tesfaye; Sheen, Faye; Zhang, Yanfeng; US9181262; (2015); B2;,
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bromide – Wiktionary