In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 399-94-0, name is 1-Bromo-2,5-difluorobenzene belongs to bromides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. HPLC of Formula: C6H3BrF2
2-bromo-l,4-difluorobenzene (1.5 eq.) was dissolved in 4 volumes of THF (based on weight of tert-butyl2-oxopyrrolidine-l-carboxylate) and cooled to about 5 Celsius. A solution of 2.0 M iPrMgCl in THF (1.4 eq.) was added over 2 hours to the mixture while maintaining a reaction temperature below 25 Celsius. The solution was allowed to cool to about 5 Celsius and stirred for 1 hour (GC analysis confirmed Grignard formation). A solution of tert-butyl 2-oxopyrrolidine-l-carboxylate (1.0 eq.) in 1 volume of THF was added over about 30 min while maintaining a reaction temperature below 25 Celsius. The reaction was stirred at about 5Celsius for 90 min (tert-butyl 2-oxopyrrolidine-l-carboxylate was confirmed to be less than 0.5 area % by HPLC). The reaction was quenched with 5 volumes of 2M aqueous HC1 while maintaining a reaction temperature below 45 Celsius. The reaction was then transferred to a reparatory funnel adding 10 volumes of heptane and removing the aqueous layer. The organic layer was washed with 4 volumes of saturated aqueous NaCl followed by addition of 2×1 volume of saturated aqueous NaCl. The organic layer was solvent-switched to heptane (<1% wt THF confirmed by GC) at a distillation temperature of 35-55 Celsius and distillation pressure of 100-200 mm Hg for 2x4 volumes of heptane being added with a minimum distillation volume of about 7 volumes. The mixture wasthen diluted to 10 volumes with heptane while heating to about 55 Celsius yielded a denser solid with the mixture being allowed to cool to room temperature overnight. The slurry was cooled to less than 5 Celsius and filtered through polypropylene filter cloth. The wet cake was washed with 2x2 volumes of heptane. The solids were dried under vacuum at 55 Celsius until the weight was constant, yielding tert-butyl (4-(2,5-difluorophe-nyl)-4-oxobutyl)-carbamate as a white solid at about 75% to 85% theoretical yield.
The synthetic route of 399-94-0 has been constantly updated, and we look forward to future research findings.
Reference:
Patent; Array BioPharma, Inc.; Arrigo, Alisha B.; Juengst, Derrick; Shah, Khalid; (70 pag.)US2016/137654; (2016); A1;,
Bromide – Wikipedia,
bromide – Wiktionary