Related Products of 399-94-0, These common heterocyclic compound, 399-94-0, name is 1-Bromo-2,5-difluorobenzene, its 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.
A solution of tert-butyl pyrrolidine- 1-carboxylate (20 g, 116.8 mmol) and (- )sparteine (32.9, 140 mmol) in MTBE (360 mL) was cooled to -78 0C, and sec-BuLi (10OmL, 140 mmol, 1.4 M in cyclohexane) was introduced drop-wise via cannula, keeping the internal temperature under -70 0C. The resulting solution was stirred for 3 hours at -78 0C, followed by addition of a solution of ZnCl2 (93.4 mL, 93.4 mmol, IM in Et2O) drop-wise with rapid stirring, keeping the internal temperature below -65 0C. The resulting light suspension was stirred at -78 0C for 30 minutes and then warmed to ambient temperature. The resulting mixture was charged with 2-bromo-l,4-difluorobenzene (14.5 mL, 128 mmol), followed by Pd(OAc)2 (1.31 g, 5.8mmol) and ^-Bu3P-HBF4 (2.03 g, 7.0 mmol) in one portion. After stirring overnight at ambient temperature, 10.5 mL Of NH4OH solution was added and the reaction was stirred for another hour. The resulting slurry was filtered through CELITE and washed with Et2O (1 L). The filtrate was washed with HCl (0.5 L, IM aq.) and brine. The organic layer was filtered and concentrated, and the crude product was purified by silica column chromatography, eluting with 5-10% EtO Ac/hex anes to give product (R)-tert-butyl 2- (2,5-difluorophenyl)pyrrolidine- 1-carboxylate as yellow oil (23.9 g, 72% 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.; ANDREWS, Steven, W.; HAAS, Julia; JIANG, Yutong; ZHANG, Gan; WO2010/33941; (2010); A1;,
Bromide – Wikipedia,
bromide – Wiktionary