- Method for preparing high-purity difenidol hydrochloride
-
The invention discloses a method for preparing high-purity difenidol hydrochloride. The method comprises the following steps: after an intermediate alpha,alpha-diphenyl-1-piperidine butanol is prepared, dissolving the intermediate into one of acetone, ethyl acetate, tetrahydrofuran, butanone, acetonitrile and dichloromethane; increasing the temperature to 40-45 DEG C, adding activated carbon, andperforming uniform stirring for 0.5-1 hour; performing hot filtering, keeping the temperature of filtrate to 40-45 DEG C, dropping a hydrochloric acid solution at a speed of 2-8mL/minute till the pH value of the solution is 4-6, and continuously keeping the temperature to implement a reaction for 1-2 hours; reducing the temperature to 20-25 DEG C, keeping the temperature for 1-2 hours, further reducing the temperature to 5-10 DEG C, and performing stirring for 2-4 hours, so as to obtain difenidol hydrochloride through evolution. Not only is the preparation method disclosed by the invention simple, low in instrument and equipment requirement and low in production cost, but also the prepared target product has a small number of impurity types and has a low content of impurities, the salt formation mole yield of the product is 90% or greater, the purity is 99.8% or greater, an impurity diphenyl methanol is controlled within 0.05% or less, meanwhile, the content of alkene impurities is controlled within 0.05% or less, and the content of total impurities is 0.1% or less.
- -
-
Paragraph 0032; 0036-0055; 0065-0076
(2019/12/25)
-
- Preparation method of difenidol hydrochloride
-
The invention relates to the field of medicine, and discloses a preparation method of difenidol hydrochloride. The method comprises the following steps: S1. preparation of 1-(3-chloropropyl)hexahydro piperidine; S2. preparation of alpha,alpha-dibenzyl-1-piperidinebutanol; S3. preparation of alpha,alpha-dibenzyl-1-piperidinebutanol hydrochloride; wherein, the step S3 comprises the following preparation steps: alpha,alpha-dibenzyl-1-piperidinebutanol prepared in the step S2 is dissolved in an organic solvent, a buffer salt solution is added, the temperature is heated to 55+/-5 DEG C, active carbon is added, insulation is carried out for 1 hour, and filtering is carried out; hydrochloric acid is added into the obtained filtrate, the pH is adjusted to 5-6, the temperature is controlled at 50-60 DEG C and stirring is carried out for 25-35 minutes, filtering and drying are carried out, and alpha,alpha-dibenzyl-1-piperidinebutanol hydrochloride is obtained. Compared with the prior art, the content of related impurities in difenidol hydrochloride prepared by the preparation method is greatly reduced, especially the content of alkene compounds is reduced by 85%, content of total impurity is reduced by 90%, and safety and effectiveness of difenidol hydrochloride are effectively guaranteed in clinic application.
- -
-
Paragraph 0039; 0040
(2017/07/21)
-
