Some common heterocyclic compound, 348-57-2, name is 1-Bromo-2,4-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. HPLC of Formula: C6H3BrF2
To a clean and dry 72 L round bottom flask was added l-bromo-2,4-difluorobenzene (1586 g, (0373) 1.15 equiv, Oakwood lot H4460) and MTBE (20 L, 12.6 vol). This solution was cooled to – 70 to -75 °C and treated with n-BuLi (3286 mL, 1.15 equiv, 2.5 M in hexanes, SAFC lot 32799MJ), added as rapidly as possible while maintaining -75 to -55 °C. This addition typically required 35-45 minutes to complete. (NOTE: If the n-BuLi is added slowly, a white slurry will form and this typically gives poor results). After stirring at -70 to -65 °C for 45 minutes, a solution of compound 3-Br (2000 g, 1.0 equiv, AMRI lot 15CL049A) in MTBE (3 vol) was added rapidly (20-30 min) by addition funnel to the aryl lithium solution while maintaining -75 to -55 °C. After stirring for 30-60 minutes at -75 to -55 °C, the reaction was analyzed by GC/MS and showed only trace (0.5percent AUC) l-bromo-2,4-difluorobenzene present. The reaction was slowly quenched with aqueous 2 M HQ (3.6 L) and allowed to warm to room temperature. The mixture was adjusted to pH = 6.5 to 8.5 using NaHCC>3 (4 L), and the organic layer was separated. The MTBE layer was washed with brine (5percent NaCl in water, 4 L), dried over MgS04, filtered, and concentrated. In order to convert the intermediate hemi-acetal to 4, the crude mixture was heated inside the 20 L rotovap flask at 60-65 °C for 3 hours (under vacuum), at this point all the hemi-acetal was converted to the desired ketone 4- Br by *H NMR (CDC13). This provided crude compound 4-Br [2.36 kg, 75percent (AUC) by HPLC] as a brown oil that solidified upon standing. This material can then be used “as-is” in the next step without further purification.
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 348-57-2, its application will become more common.
Reference:
Patent; VIAMET PHARMACEUTICALS, INC.; HOEKSTRA, Willam, J.; YATES, Christopher, M.; WO2015/143142; (2015); A1;,
Bromide – Wikipedia,
bromide – Wiktionary