Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 399-94-0, name is 1-Bromo-2,5-difluorobenzene, A new synthetic method of this compound is introduced below., Application In Synthesis of 1-Bromo-2,5-difluorobenzene
To a solution of 2-bromo-l,4-difluoro-benzene (3.01 g, 15.60 mmol, 1.20 Eq) in THF (15 mL) was added isopropyimagnesium chloride complex (2.27 g, 15.60 mmol, 1.20 Eq) at 0C dropwise under N2. The reaction was stirred at 15C for 1 hr to prepare (2, 5-difluorophenyl) magnesium bromide (23 mL). To a solution of tert-butyl (R)-4-((tert-butyldiniethyl.silyl)oxy)-2- oxopyrrolidine-l-carboxylate (4.10 g, 13.00 mmol, 1.00 Eq) in THF (50 mL) was added (2,5- difluorophenyl) magnesium bromide (23 mL) dropwise at ()C over 30 mins. The reaction mixture was stirred at 0C for 1 hr. Methanol (20 mL) was added to the mixture followed by NaBH4 (738 mg, 19.50 mmol, 1.50 Eq) at 0C. The mixture was stirred at 0C for 1 hr then poured into 10% aqueous NH4CI. The mixture was extracted with EtOAc (20 mL*2), the combined organic layers were washed with brine, dried over Na2S04, filtered and concentrated. The crude product was purified by medium pressure liquid chromatography (MPLC) to give tert-butyl ((2R)-2-((tert- butyldimethylsilyl)oxy)-4-(2,5-difluorophenyl)-4-hydroxybutyl)carbamate (2.22 g, 5.14 mmol, 39.6% yield). 1H-NMR (400 MHz, CDC13) delta ppm 7.17-7.15 (m, 1H), 6.86-6.79 (m, 2H), 5.11-5.06 (m, 1H), 4.70 (br.s, 1H), 4.02-3.98 (m, 1H), 3.69 (br.s, 0.5H), 3.46 (br.s, 0.5H), 3.33-3.14 (m, 2H), 1.80-1.69 (m. 2H), 1.35 (s. 9H), 0.84-0.82 (9H, m), 0.04-0.03 (6H, m).
The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.
Reference:
Patent; BLUEPRINT MEDICINES CORPORATION; WENGLOWSKY, Steven, Mark; BROOIJMANS, Natasja; MIDUTURU, Chandrasekhar, V.; BIFULCO, Neil; (206 pag.)WO2017/35354; (2017); A1;,
Bromide – Wikipedia,
bromide – Wiktionary