AU2016102180A4

AU2016102180A4 - Farrerol drug intermediates 2,6-dimethyl-acetanilide synthesis method

Info

Publication number: AU2016102180A4
Application number: AU2016102180A
Authority: AU
Inventors: donghong chu
Original assignee: Xiamen An Pu Dun Information Technology Co Ltd
Current assignee: Xiamen An Pu Dun Information Technology Co Ltd
Priority date: 2015-12-23
Filing date: 2016-12-22
Publication date: 2017-02-16
Anticipated expiration: 2024-12-22

Abstract

Farrerol drug intermediates 2,6-dimethyl-acetanilide synthesis method, comprising the following steps: equipped with a stirrer, a thermometer, a reflux condenser and a dropping funnel, the reaction vessel was added 1.Imol 2,6-dimethylaniline solution (2), controlling the stirring speed 120-140rpm, added dropwise 1.5-1.53mol phenylacetaldehyde solution ( 3), control the temperature of the solution at 115-119 C, after the completion of dropwise addition, the solution temperature was increased to 126--129 C, it was completely dissolved, continued the reaction for 40-50min, added 400ml sodium chloride solution, precipitation solid, reducing the solution temperature to 35--38 C, suction filtered, washed with salt solution until the pH was 8-9, dehydrated with dehydrating agent, recrystallized from ether solution got 2,6-dimethyl-acetanilide .

Description

Farrerol drug intermediates 2,6-dimethyl-acetanilide synthesis method

TECHNICAL FIELD

The present invention relates to farrerol drug intermediates 2,6-dimethyl-acetanilide synthesis method.

BACKGROUND ART

Farrerol drugs is mainly used for clearing in the respiratory mucosa, and promoting cilia movement, strengthen the trachea, bronchus foreign body mechanical features that make fiber breakage glycoprotein sialic acid content decreased, chronic bronchitis patient's exact effect, which have lasting effect and stability. 2,6-dimethyl-acetanilide as Farrerol drug intermediates, its synthesis method is of great economic significance for improving drug synthesis product quality, reducing the by-product content.

SUMMARY OF THE INVENTION

Object of the present invention is to provide farrerol drug intermediates 2,6-dimethyl-acetanilide synthesis method, comprising the following steps: (i) equipped with a stirrer, a thermometer, a reflux condenser and a dropping funnel, the reaction vessel was added 1.1 mol 2,6-dimethylaniline solution (2), controlling the stirring speed 120-140rpm, added dropwise 1.5-1.53mol phenylacetaldehyde solution (3), control the temperature of the solution at 115—119 °C, after the completion of dropwise addition, the solution temperature was increased to 126-129 °C, it was completely dissolved, continued the reaction for 40-50min, added 400ml sodium chloride solution, precipitation solid, reducing the solution temperature to 35—38 °C, suction filtered, washed with salt solution until the pH was 8-9, dehydrated with dehydrating agent, recrystallized from ether solution , got 2,6-dimethyl-acetanilide; wherein, sodium chloride solution in step (i) has a mass fraction of 25-35%; salt solution in step (i) is any one of potassium nitrate solution or sodium bromide solution; dehydrating agent in step (i) is any one of anhydrous sodium sulfate or anhydrous magnesium sulfate; ether solution in step (i) has a mass fraction of 95-98%.

The throughout reaction process can be summarized using the following reaction formula:

(2) ¢3) {1)

Advantage of the present invention is that: the reaction intermediate links are reduced, reducing the reaction temperature and reaction time, improving the reaction yield.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS OF THE INVENTION

Embodiment 1

Equipped with a stirrer, a thermometer, a reflux condenser and a dropping funnel, the reaction vessel was added 1.1 mol 2,6-dimethylaniline solution (2), controlling the stirring speed 120 rpm, added dropwise 1.5 mol phenylacetaldehyde solution ( 3), control the temperature of the solution at 115 °C, after the completion of dropwise addition, the solution temperature was increased to 126 °C, it was completely dissolved, continued the reaction for 40 min, added 400ml sodium chloride solution with a mass fraction of 25%, precipitation solid, reducing the solution temperature to 35 °C, suction filtered, washed with potassium nitrate solution until the pH was 8-9, dehydrated with anhydrous sodium sulfate dehydrating agent, recrystallized from ether solution with a mass fraction of 95% , got 2,6-dimethyl-acetanilide 148.82 g, yield 83%.

Embodiment 2

Equipped with a stirrer, a thermometer, a reflux condenser and a dropping funnel, the reaction vessel was added 1.1 mol 2,6-dimethylaniline solution (2), controlling the stirring speed 130 rpm, added dropwise 1.5 mol phenylacetaldehyde solution ( 3), control the temperature of the solution at 117 °C, after the completion of dropwise addition, the solution temperature was increased to 127 °C, it was completely dissolved, continued the reaction for 45 min, added 400ml sodium chloride solution with a mass fraction of 28%, precipitation solid, reducing the solution temperature to 36 °C, suction filtered, washed with sodium bromide solution until the pH was 8, dehydrated with anhydrous sodium sulfate dehydrating agent, recrystallized from ether solution with a mass fraction of 96% , got 2,6-dimethyl-acetanilide 154.20 g, yield 86%.

Embodiment 3

Equipped with a stirrer, a thermometer, a reflux condenser and a dropping funnel, the reaction vessel was added 1.1 mol 2,6-dimethylaniline solution (2), controlling the stirring speed 140 rpm, added dropwise 1.53 mol phenylacetaldehyde solution ( 3), control the temperature of the solution at 119 °C, after the completion of dropwise addition, the solution temperature was increased to 129 °C, it was completely dissolved, continued the reaction for 50 min, added 400ml sodium chloride solution with a mass fraction of 25%, precipitation solid, reducing the solution temperature to 35 °C, suction filtered, washed with potassium nitrate solution until the pH was 9, dehydrated with anhydrous sodium sulfate dehydrating agent, recrystallized from ether solution with a mass fraction of 98% , got 2,6-dimethyl-acetanilide 163.16 g, yield 91%.

While a number of preferred embodiments have been described, it will be appreciated by persons skilled in the art that numerous variations and/or modifications may be made to the invention without departing from the spirit or scope of the invention as broadly described. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive.

Claims

1. Farrerol drug intermediates 2,6-dimethyl-acetanilide synthesis method, comprising the following steps: (i) equipped with a stirrer, a thermometer, a reflux condenser and a dropping funnel, the reaction vessel was added 1.1 mol 2,6-dimethylaniline solution (2), controlling the stirring speed 120-140rpm, added dropwise 1.5-1.53mol phenylacetaldehyde solution (3), control the temperature of the solution at 115—119 °C, after the completion of dropwise addition, the solution temperature was increased to 126—129 °C, it was completely dissolved, continued the reaction for 40-50min, added 400ml sodium chloride solution, precipitation solid, reducing the solution temperature to 35—38 °C, suction filtered, washed with salt solution until the pH was 8-9, dehydrated with dehydrating agent, recrystallized from ether solution , got 2,6-dimethyl-acetanilide; wherein, sodium chloride solution in step (i) has a mass fraction of 25-35% .

2. Farrerol drug intermediates 2,6-dimethyl-acetanilide synthesis method according to claim 1 wherein salt solution in step (i) is any one of potassium nitrate solution or sodium bromide solution.

3. Farrerol drug intermediates 2,6-dimethyl-acetanilide synthesis method according to claim 1 wherein dehydrating agent in step (i) is any one of anhydrous sodium sulfate or anhydrous magnesium sulfate.

4. Farrerol drug intermediates 2,6-dimethyl-acetanilide synthesis method according to claim 1 wherein ether solution in step (i) has a mass fraction of 95-98%.