Application of 399-94-0, A common heterocyclic compound, 399-94-0, name is 1-Bromo-2,5-difluorobenzene, molecular formula is C6H3BrF2, 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.
Reference Example-71 THF (25 mL) was added to metal magnesium (2.55 g, 105 mmol), and 2-bromo-1,4-difluoro benzene (19.70 g, 100 mmol) was slowly added thereto, whereby a Grignard reagent was prepared. The previously prepared Grignard reagent was added dropwise to the separately prepared solution of diethyl oxalate (15.34 g, 105 mmol) in THF (10 mL) at -40 C. or lower. After the dropping was completed, the reaction temperature was raised to 0 C., followed stirring for 1 hour. A saturated ammonium chloride aqueous solution and water (200 mL) were added to the reaction solution, and the resultant product was extracted with ethyl acetate (200 mL*2). After the organic layer was dried over magnesium sulfate and filtered, the solvent was distilled off under reduced pressure, and the resultant product was distilled under reduced pressure, whereby ethyl 2-(2,5-difluorophenyl)-2-oxoacetate (14.82 g, yield: 62%) was obtained as a colorless liquid. 1H-NMR (400 MHz, CDCl3): delta1.40 (t, J=7.0 Hz, 3H), 4.44 (q, J=7.0 Hz, 2H), 7.16 (ddd, J=9.3, 9.3 and 4.0 Hz, 1H), 7.34 (dddd, J=9.3, 9.2, 7.3 and 3.3 Hz, 1H), 7.60 (ddd, J=8.2, 5.3 and 3.3 Hz, 1H). 19F-NMR (376 MHz, CDCl3): delta-116.9 (d, J=7.8 Hz, 1F), -116.3 (d, J=7.8 Hz, 1F).
The synthetic route of 399-94-0 has been constantly updated, and we look forward to future research findings.
Reference:
Patent; KAKEN PHARMACEUTICAL CO., LTD.; SAGAMI CHEMICAL RESEARCH INSTITUTE; KOBAYASHI, Osamu; NIIKURA, Naoko; INOUE, Tomoko; MIZUTA, Satoshi; TAKATSUNA, Reiko; HIRAI, Kenji; SHIROUZU, Kentaro; OBATA, Miyoo; (183 pag.)US2016/24110; (2016); A1;,
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