Reference of 327-52-6, In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 327-52-6 as follows.
In a 5L dry reaction flask, dried 1.5kg of tetrahydrofuran and 40g of 2-chloropropane were added, and the temperature was raised to microfluidic (60C), then, 5 ml of isopropylmagnesium chloride was added dropwise to initiate the reaction, after the reaction is stable, the remaining 2-chloropropane 350g was slowly added drop wise, and the temperature was controlled to maintain micro reflux (68-72), and reflux was added dropwise for 2 hours (until complete reaction of magnesium chips, if any magnesium chips were left, 2-chloropropane was added. ), cooled to room temperature after the reaction, in a 30L reactor, 1.3kg of dried tetrahydrofuran, 1.3kg of toluene and 682g of trifluorobromobenzene were added, and the nitrogen protection of the reaction solution was lowered to a temperature of -25C, the temperature is controlled below -20C, and 2kg of isopropylmagnesium chloride was added dropwise, the incubation reaction was completed for one hour after dropping, monitored by HPLC, cuprous chloride 24g was added, then , heated and stirred for 30 minutes, a solution of 0.5 kg of a solution of compound 3 (512 g) in toluene was added dropwise, the reaction was carried out from minus 5C to minus 2C for 16 hours, monitored by HPLC, kg of saturated aqueous ammonium chloride solution (quenching effect) was added dropwise below 5C, the temperature was controlled below 10C, and about 1.5 kg of 3N hydrochloric acid was added dropwise to adjust the pH to approx 4. The aqueous phase was extracted once with 0.5L of toluene, the organic phases were combined and washed once with diluted aqueous ammonia (concentrated aqueous ammonia 100g watered with 0.5kg) and washed twice with 0.5kg semi-saturated brine, the aqueous phase was combined and extracted once with 0.5kg toluene, and toluene was distilled under reduced pressure at 45-55C, when the reaction liquid becomes a paste, 2 kg of water was added, concentration was continued until the distilled out solvent was water. 1kg of methanol was added, beaten overnight, and filtered, filter cake was washed twice with water, and the product was dried by blowing at 65C to obtain Compound 4 (720g) as a pale yellow powder in a yield of 85%.
According to the analysis of related databases, 327-52-6, the application of this compound in the production field has become more and more popular.
Reference:
Patent; Heding (Nanjing) Pharmaceutical Co., Ltd.; Li Wensen; (18 pag.)CN107540575; (2018); A;,
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