Reference of 53005-44-0,Some common heterocyclic compound, 53005-44-0, name is 2-Methoxy-6-methylbenzonitrile, molecular formula is C9H9NO, 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.
To a solution of 2-bromo-3-methylphenol (10.0 g, 53.5 mmol) in DMF (60 ml) was added sodium hydride (2.78 g, 69.5 mmol) in small portions at 0 C, which was followed by addition of Mel (6.69 mL, 107 mmol). TLC showed formation of a slightly less polar spot right away. The reaction was diluted with EtOAc (400 mL), washed with water 3 times, dried over Na2S04, and concentrated. The crude product was used in the next step without further purification. To the flask charged with the above material and a stir bar was added CuCN (9.9 g, 109 mmol) and DMF (100 mL). The mixture was purged three times with nitrogen, and heated to 150 C for 24 hours. TLC showed formation of a more polar spot. . The reaction was cooled to RT, diluted with DCM (400 mL), and filtered through a pad of celite to remove the solids. The filtrate was washed with saturated NH4Oac and brine, dried over sodium sulfate, concentrated to afford a brownish solid (4.8g, 60% yield). The resulting nitrile was used in the following step without further purification. To a flask charged with the nitrile and a stir bar was added NBS (6.4 g, 36 mmol) and TFA (60 mL). The reaction was allowed to stir at RT for 16 hours. TLC showed clean formation of a slightly more polar spot. The solvent was removed under vacuum, and the residue was purified by silica gel flash chromatography. After removal of solvent, 3-bromo-6-methoxy-2-methylbenzonitrile was collected.
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-Methoxy-6-methylbenzonitrile, its application will become more common.
Reference:
Patent; MERCK SHARP & DOHME CORP.; PIO, Barbara; PASTERNAK, Alexander; SHAHRIPOUR, Aurash; TANG, Haifeng; WALSH, Shawn; WO2013/90271; (2013); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts