In the previous article, we talked about the preparation method of intermediate 2 in the preparation of tetracaine hydrochloride, this time we continue our operation steps:
(1) Add 600g of deionized water to the bottle, add 65g of deionized membrane Hydroxide Warner while stirring, and stir until the solution is clear after adding, cool down to room temperature, and stop stirring for use.
(2) Add 500 g of methanol, add 250 g of intermediate II, and cool with a water bath.
(3) After the heat preservation is completed, start to evaporate the methanol under reduced pressure, and the maximum temperature shall not exceed 70 degree .
(4) After the concentration is completed, Case adds hydrochloric acid for adjustment.
(5) The pH value is about 34, stop dripping, stir for one hour, carry out suction filtration, and finally get about 300g of off-white solid.
(6) When the temperature of drying material is less than 50 degree , about 210220g of material is obtained
Crude product preparation and refining:
(1) Add 1000 g of methyl isobutyl ketone, after pumping, close the vacuum and open the kettle mouth, let it stand for 30 minutes, and cluster the lower water layer. 130 g of intermediate three and 175 g of sodium carbonate were put in.
(2) Heat up to reflux to separate water. The water separation time is about six hours.
(3) After aliquoting water, add the intermediate one. The reflux reaction is carried out, and water separation is carried out at the same time.
(4) When no more water comes out, cool down to 5566 degree , add deionized water, and let stand for stratification for an hour. At this time, the temperature is about 50 degree .
(5) Methyl isobutyl ketone was evaporated from the organic layer under reduced pressure until almost no fractions appeared at 90 degree , and the solvent was removed under reduced pressure.
(6) Weigh 75g of hydrochloric acid, slowly drip it with a constant pressure dropping funnel, and control the internal temperature to be between 6075 degree . The water pump pumps about 30g of water brought in by hydrochloric acid, stops pumping, and controls the pumping temperature between 60 and 75 degree .
Post-processing process:
(1) Add 170 g of ethanol, turn on the heating and dissolve it completely, remove the heating, cool with ice water, drop to 510 degree , filter with suction, rinse the filter cake with a small amount of cold alcohol once, dry it, and weigh to obtain 123 g of solid.
(2) Decolorize, add 123g of crude product, add 9g of activated carbon, add 150g of ethanol, heat, stir and reflux for 20 minutes, after reflux is completed, filter the activated carbon while hot, and transfer the filtrate after pumping to a clean 500ml three-necked flask.
(3) Open the three-necked flask and stir, let it naturally cool down to 30 degree , cool down with an ice bath, and filter with suction when it drops to 5 degree , and rinse the filter cake once with a small amount of cold ethanol. After rinsing, the materials dried by suction filtration were transferred to filter paper and dried in an oven to obtain 110g of product, which was qualified after laboratory analysis and put into storage. The preparation process of the whole product is complicated, rigorous, and interlocking. The content of the product produced is more than 98 percent , which meets the requirements of product quality.
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