| 95% |
|
2-amino-3,5-dibromobenzyl alcohol 2 g (about 7.12 mmol) was added to 15 ml of tetrahydrofuran (THF)At 0-5 C and under stirring conditions,Slowly, in part by adding solid phosgene (triphosgene) 722g, the use of sodium bicarbonate solution absorption system generated HC1,After reaction at 0-5 C for 2 hours,Under stirring conditions,0.9 g of N-methylcyclohexane was slowly added and reacted at room temperature,TLC detection reaction material disappeared,Slowly add 2N hydrochloric acid ethanol solution,The pH of the conditioning system is between 5.5 and 6.0, crystallized at 0 C,To obtain 2.79 g of fresh bromine hydrochloride, as an off-white powder,The yield in terms of 2-amino-3,5-dibromobenzyl alcohol was 95%, the purity was 99.5% by HPLC, |
| 80% |
|
Adding 4.84kg of N-methylcyclohexylamine and 0.44kg of toluene to a 30L glass reactor with a water separator5.0 kg of 3,5-dibromo-2-aminobenzyl alcohol, 0.5 kg of solid super acid SiO2-OSO3H (SSA), 1.2 kg of acetic acid, and then heated to 85 C for a total of 12 hours after stirring.Sampling UPLC test (take the reaction solution as a sample at a concentration of approximately 275 mg/ml).After passing the reaction (3,5-dibromo-2-aminobenzyl alcohol is not more than 5.0%), it is concentrated under reduced pressure until no significant fraction is distilled off, and the residue is transferred to a barrel and cooled to room temperature, and then 12 kg of acetone is added.The solution was then transferred to a 100 L double-layer glass reactor and adjusted to pH 2 - 3 with 15% hydrochloric acid to precipitate a solid. After 20 minutes,Repeat the measurement of pH 2 ~ 3; continue to stir for 1 hour, then continue to cool to 0 C for 4 hours, centrifugal filtration, to obtain bromohexine hydrochloride wet,The wet product is placed in a blast drying oven tray, dried at 35±5C, and turned once every 3 hours.After drying for 10 hours, 6.24 kg was obtained after the water was qualified, and the yield was 85%. Bromohexidine hydrochloride refined: Adding 42.0 kg of 95% ethanol and 6.2 kg of crude bromohexidine hydrochloride to a 100 L enamel reactor.The temperature was raised to reflux, stirred and dissolved, and then 0.15 kg of activated carbon was added, and the mixture was decolorized by stirring for 1 hour.The titanium rod was filtered, and the filtrate was transferred to a 100 L double-layer glass reactor and slowly cooled to room temperature.Then, the crystallized mixture was stirred at room temperature for 2 hours, and then cooled to 5 C and stirred for 5 hours.The mixture was filtered by centrifugation, and the filter cake was rinsed with a small amount of 95% ethanol to obtain bromohexine hydrochloride wet product.The bromohexine hydrochloride wet product is placed in a vacuum drying oven tray and dried at 60 C, and the degree of vacuum is less than -0.08 mPa.The material was turned over once every 2 hours, dried for 12 hours, and the water was qualified to receive 4.96 kg, and the yield was 80%. |
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