1-broMo-5-fluoro-2-Methyl-4-nitrobenzene synthesis

Yield: 54.3%

Reaction Conditions:

with sulfuric acid;potassium nitrate at 0 - 25; for 2 h;Inert atmosphere;

Steps:

3 Preparation of the compound of formula 4
The compound of formula 3 (5.0 g, 26.5 mmol, 1.0 equiv) and 98% concentrated sulfuric acid (50 ml) were added to a 100 ml three-necked flask.The solution was cooled to 0 ° C to 5 ° C and potassium nitrate (3.5 g, 34.6 mmol, 1.3 equiv) was added in portions.And reacted at 25 ° C for 2 hours under nitrogen protection. After completion of the reaction, the reaction solution was poured into a large amount of ice water,Ethyl acetate extraction. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, Concentrate under reduced pressure. The crude product was purified by silica gel column chromatography (petroleum ether) to give 3.4 g of the compound of formula 4 as a yield of 54.3%.

References:

Shanghai Acebright Pharmaceuticals Group Co., Ltd.;Yu, Libing;Guo, Maojun;Yang, QinGang;Liu, Huixin CN105646333, 2016, A Location in patent:Paragraph 0136-0139