1-Bromo-3-fluoro-5-methylbenzene synthesis

Yield:202865-83-6 76%

Reaction Conditions:

Stage #1:2-bromo-6-fluoro-4-methyl aniline with hydrogenchloride;sodium nitrite in water;acetonitrile at 0; for 1 h;
Stage #2: with potassium iodide in water;acetonitrile at 0 - 20;

Steps:

31.2 Step 2) Synthesis of 1 -bromo-3 -fluoro-5 -methylbenzen
2-Bromo-6-fluoro-4-methylaniline (11.2 g, 55 mmol), diluted hydrochloric acid (28.5 mL, 6 M) and acetonitrile (300 mL) were added to a 500 mL single-neck flask, then to the mixture in flask was added dropwise slowly a solution of sodium nitrite (5.69 g, 82.4 mmol) in water (40 mL) at 0 °C. After the addition, the reaction mixture was stirred at 0 °C for 1 h, then to the flask was added a solution of potassium iodide (18.3 g, 110 mmol) in water (30 mL). After the addition, the mixture was stirred at 0 °C for 0.5 h, then stirred at rt overnight.To the reaction mixture was added saturated aqueous sodium sulfite (300 mL), and the resulting mixture was concentrated in vacuo to remove acetonitrile. The residue was extracted with ethyl acetate (100 mL x 2), and the organic layers were combined. The combined organic layers were washed with saturated brine (100 mL), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated in vacuo. The residue was purified by silica-gel column chromatography (ethyl acetate/petroleum ether (v/v) = 1/100) to give the title compound as a white solid (13.2 g, 76%).‘H NIVIR (400 MHz, CDC13) (ppm): 7.29 (s, 1H), 6.81 (d,J= 8.4 Hz, 1H), 2.31 (s, 3H).

References:

SUNSHINE LAKE PHARMA CO., LTD.;YANG, Xinye;HUANG, Changwei;MA, Facheng;ZHANG, Ji;WANG, Xiaojun;ZHANG, Yingjun WO2017/36404, 2017, A1 Location in patent:Page/Page column 124

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