Synthesis method of 3-methylamino-1, 2-propylene glycol

Abstract

The invention discloses a synthesis method of high-purity 3-methylamino-1, 2-propylene glycol, and high-purity methylamino glycerin can be prepared by the steps of hydrolyzing epoxy chloropropane, amination, dehydration, alkalization, filtering, separating methanol, distilling finished product and the like, wherein the amination is carried out under the condition of adding catalyst, and the reaction is carried out for 2-3h under the condition of 45-55 DEG C and 0-0.025MPa. The methylamino glycerin product prepared by the invention is colorless and transparent, has high product purity reaching up to more than 99.5% (GC); and the synthesis method adopts molecular distillation so as to greatly shorten the distillation time of the methylamino glycerin, and adopts the catalyst so as to shorten the reaction time and the production period and improve the production efficiency, thus being more suitable for industrialized production.

Description

technical field

[0001] The invention relates to a pharmaceutical intermediate, in particular to a method for synthesizing 3-methylamino-1,2-propanediol. Background technique

[0002] 3-methylamino-1,2-propanediol (hereinafter referred to as methylaminoglycerol) is an important intermediate for the production of a new generation of X-CT non-ionic contrast agent iopromide, which is mainly used in clinical angiography, Renal arteriography, urography, CT contrast-enhanced examination, body cavity display (arthrography, hysterosalpingography, Loudunography), with high contrast density, low toxicity, good systemic and local body tolerance, and side effects It is considered to be one of the best non-ionic contrast agents at present because of its outstanding advantages such as low rate, wide application population, mild or almost no adverse reactions. The purity of methylaminoglycerol directly affects the internal quality and clinical application effect of iopromide. Since the adv...

Examples

Embodiment 1

[0024] (1) Epichlorohydrin hydrolysis: 1.6 kilograms of sulfuric acid and 500 kilograms of deionized water are pumped into a 1000 L glass-lined reactor with a stirrer, and the reactor is started to stir. Heat the contents of the kettle. Heat the material to 70-80°C within 30-60 minutes. Add 400 kg of epichlorohydrin into the reactor within 3 to 5 hours, and control the reaction temperature to 90 to 105°C. After the reaction is completed, lower the temperature. When the temperature in the kettle drops to 20-50° C., add 30-50 kg of 10-15% sodium hydroxide solution into the reaction kettle and stir for 30-60 minutes. Turn on the steam to heat up, and steam the water in the kettle. When the gas phase temperature reaches 98-103°C, turn on the vacuum pump. Under the condition of vacuum degree ≥ 0.099MPa, the condensed liquid with a gas phase temperature of 115-125°C is taken as an intermediate product.

[0025] (2) Ammonification: Add 1500 kg of prepared monomethylamine aqueous ...

Embodiment 2

[0033] (1) Epichlorohydrin hydrolysis: 1.4 kilograms of sulfuric acid and 380 kilograms of deionized water are sucked into a 1000 L glass-lined reactor with a stirrer airtight, and the reactor is started to stir. Heat the contents of the kettle. Heat the material to 70-80°C within 30-60 minutes. Add 300 kg of epichlorohydrin to the reaction kettle within 3 to 5 hours, and control the reaction temperature to 90 to 105°C. After the reaction is complete, lower the temperature. When the temperature in the kettle drops to 20-50° C., add 35 kilograms of 15% sodium hydroxide solution into the reaction kettle and stir for 30-60 minutes. Turn on the steam to raise the temperature, and steam the moisture in the reaction kettle. When the gas phase temperature reaches 98-103°C, turn on the vacuum pump. Under the condition of vacuum degree ≥ 0.099MPa, the condensed liquid with a gas phase temperature of 115-125°C is taken as an intermediate product.

[0034] (2) Ammonification: Add 130...

technical field

[0001] The invention relates to a pharmaceutical intermediate, in particular to a method for synthesizing 3-methylamino-1,2-propanediol. Background technique

[0002] 3-methylamino-1,2-propanediol (hereinafter referred to as methylaminoglycerol) is an important intermediate for the production of a new generation of X-CT non-ionic contrast agent iopromide, which is mainly used in clinical angiography, Renal arteriography, urography, CT contrast-enhanced examination, body cavity display (arthrography, hysterosalpingography, Loudunography), with high contrast density, low toxicity, good systemic and local body tolerance, and side effects It is considered to be one of the best non-ionic contrast agents at present because of its outstanding advantages such as low rate, wide application population, mild or almost no adverse reactions. The purity of methylaminoglycerol directly affects the internal quality and clinical application effect of iopromide. Since the adv...

Examples

Embodiment 1

[0024] (1) Epichlorohydrin hydrolysis: 1.6 kilograms of sulfuric acid and 500 kilograms of deionized water are pumped into a 1000 L glass-lined reactor with a stirrer, and the reactor is started to stir. Heat the contents of the kettle. Heat the material to 70-80°C within 30-60 minutes. Add 400 kg of epichlorohydrin into the reactor within 3 to 5 hours, and control the reaction temperature to 90 to 105°C. After the reaction is completed, lower the temperature. When the temperature in the kettle drops to 20-50° C., add 30-50 kg of 10-15% sodium hydroxide solution into the reaction kettle and stir for 30-60 minutes. Turn on the steam to heat up, and steam the water in the kettle. When the gas phase temperature reaches 98-103°C, turn on the vacuum pump. Under the condition of vacuum degree ≥ 0.099MPa, the condensed liquid with a gas phase temperature of 115-125°C is taken as an intermediate product.

[0025] (2) Ammonification: Add 1500 kg of prepared monomethylamine aqueous ...

Embodiment 2

[0033] (1) Epichlorohydrin hydrolysis: 1.4 kilograms of sulfuric acid and 380 kilograms of deionized water are sucked into a 1000 L glass-lined reactor with a stirrer airtight, and the reactor is started to stir. Heat the contents of the kettle. Heat the material to 70-80°C within 30-60 minutes. Add 300 kg of epichlorohydrin to the reaction kettle within 3 to 5 hours, and control the reaction temperature to 90 to 105°C. After the reaction is complete, lower the temperature. When the temperature in the kettle drops to 20-50° C., add 35 kilograms of 15% sodium hydroxide solution into the reaction kettle and stir for 30-60 minutes. Turn on the steam to raise the temperature, and steam the moisture in the reaction kettle. When the gas phase temperature reaches 98-103°C, turn on the vacuum pump. Under the condition of vacuum degree ≥ 0.099MPa, the condensed liquid with a gas phase temperature of 115-125°C is taken as an intermediate product.

[0034] (2) Ammonification: Add 130...