Tetracaine hydrochloride is a compound and a molecular weight of 264.36326. It is a white powder, easily soluble in water and soluble in ethanol.
Last time we talked about the preparation of intermediate 1, N, N-dimethylethanolamine hydrochloride, this time, we will continue the preparation of intermediate 2 in the preparation of tetracaine hydrochloride.
(1) Weigh 165g of benzocaine, add it to the bottle, weigh 139g of bromobutane and pour it into the bottle, and finally add 58g of sodium carbonate to the bottle.
(2) Install a 0~200°C thermometer, agitator, and a constant pressure dropping funnel. A reflux condenser is added to the top of the constant pressure dropping funnel, and the heating is turned on. When the internal temperature reaches 80°C, the stirring is turned on, the heating is continued, and the temperature is allowed to rise to above 90°C.
(3) Incubate the reaction at 90~95°C for four hours, 95~115°C for four hours, and finally react at 115~120°C for 2~3 hours, and return bromobutane to the reaction system in time during the reaction.
(4) After the reaction is completed, change the reflux device to a vacuum desolventizing device to remove the remaining bromobutane in the system under reduced pressure. Distilled.
(5) Weigh 160g of water and transfer it to a constant pressure dripping leak, slowly add it dropwise to the remaining reaction solution, control the internal temperature between 65 and 75°C, stir for 20 minutes, stand still for 20 minutes, and use a separatory funnel. The lower aqueous sodium carbonate phase was separated, and the upper organic phase was transferred to the reaction flask.
(6) Pickling for the first time: weigh 120g of water and 5g of hydrochloric acid, transfer them to a three-necked flask, turn on the heating, keep the internal temperature at about 70~80℃, stir for 10 minutes, measure the pH value of 2~3, and stand still for 30 minutes, the lower organic phase was collected in a beaker, and then the upper acid solution was separated.
(7) Pickling for the second time: transfer the organic phase to the reaction flask, add 120g of water, 3g of hydrochloric acid, heat up to 70-80°C, stir for 10 minutes, stand still for 30 minutes, release the lower organic phase, weigh, The average mass is between 180~200g.
(8) According to the mass ratio of ethanol: organic phase = 0.7:1, add 120~140g of ethanol, add all the materials into a 1L reaction flask, turn on the heating to dissolve, completely dissolve at 60 °C, then cool down to below 10 °C, suction filtration, filter The cake was rinsed once with cold ethanol. Drying and weighing, this step can obtain 120~125g of intermediate II (gas phase content is greater than 95%)
The preparation of intermediate 2 is over, and we can talk about the preparation method of intermediate 3 and the final preparation and purification of the final tetracaine hydrochloride as well as the subsequent processing technology.