AU2018101110A4

AU2018101110A4 - Stomach rehabilitation drug intermediate diphenylglycolic acid synthesis method

Info

Publication number: AU2018101110A4
Application number: AU2018101110A
Authority: AU
Inventors: ruer liao
Original assignee: Chengdu Ka Di Fu Technology Co Ltd
Current assignee: Chengdu Ka Di Fu Technology Co Ltd
Priority date: 2017-08-21
Filing date: 2018-08-11
Publication date: 2018-09-06
Anticipated expiration: 2026-08-11
Also published as: CN108238895A; GB201714075D0

Abstract

Stomach rehabilitation drug intermediates diphenylglycolic acid synthesis method Abstract The present invention discloses stomach rehabilitation drug intermediate diphenylglycolic acid synthesis method, comprises the following steps: 1,2-diphenyl-2-methoxyethanol and potassium chloride solution are added to the reaction vessel, the stirring speed is controlled, the temperature of the solution is 10 controlled, reacts, the benzyl salicylate solution is added in batches, the temperature of the solution is raised; cobalt acetylacetonate powder is added, continues to react, the temperature is reduced, the solution layers, washed with sodium sulfate solution for several times, washed with triethylene glycol solution for several times, washed with undecane solution for several times, recrystallizes form the triethylene glycol 15 dimethyl ether solution, dehydrates with dehydration, gets the finished diphenylglycolic acid. Figure 1 ' I ' I I ' I ' I I ' I ' I ' I ' I 200 180 160 140 120 100 80 60 40 20 0 rpm Figure 1 Figure 2

Description

The present invention discloses stomach rehabilitation drug intermediate diphenylglycolic acid synthesis method, comprises the following steps: l,2-diphenyl-2-methoxyethanol and potassium chloride solution are added to the reaction vessel, the stirring speed is controlled, the temperature of the solution is 10 controlled, reacts, the benzyl salicylate solution is added in batches, the temperature of the solution is raised; cobalt acetylacetonate powder is added, continues to react, the temperature is reduced, the solution layers, washed with sodium sulfate solution for several times, washed with triethylene glycol solution for several times, washed with undecane solution for several times, recrystallizes form the triethylene glycol 15 dimethyl ether solution, dehydrates with dehydration, gets the finished diphenylglycolic acid.

Figure 1

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200 180 160 140 120 100 80 60 40 20 0 ppm

Figure 1 ⁴\^³

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Figure 2 ι

2018101110 11 Aug2018

Stomach rehabilitation drug intermediate diphenylglycolic acid synthesis method

FIELD OF THE INVENTION

The present invention relates to a method for preparing a pharmaceutical intermediate which belongs to the field of organic synthesis, more particularly, relates to stomach rehabilitation drug intermediate diphenylglycolic acid synthesis method.

GENERAL BACKGROUND

Diphenylglycolic acid is mainly used in the preparation of stomach rehabilitation 10 drug intermediates, measuring for zirconium. It is used as organic synthesis intermediates; used as pharmaceutical raw materials, and for production of urinary system and digestive system analgesic, antispasmodic drugs. Most of the existing synthesis methods are using the process that benzoin is oxidized and transduced. Benzoin is oxidized by nitric acid to give dibenzoyl, which is added to sodium 15 hydroxide solution, reacted at 100-110 °C for 6 h, diluted with water, and then adjusted pH to 3.5 to 4 with dilute sulfuric acid. Remove the oil slick, adding activated carbon for decolorization about 0.5h, filter, adding sulfuric acid to filtrate, adjust the pH to 2, rejection filter, washing, drying for the finished product. This method of synthesis requires the use of nitric acid, sodium hydroxide solution, 20 sulfuric acid solution as reactants, due to nitric acid, sodium hydroxide solution, sulfuric acid solution attributes to corrosive solution, the requirements of equipment corrosion resistance are higher, resulting in increased production costs, and the synthesis method is complicated and the final yield is not very high. Therefore, it is necessary to propose a new synthesis method.

SUMMARY

Based on the technical problems of the background technology, the purpose of the present invention is to provide stomach rehabilitation drug intermediate diphenylglycolic acid synthesis method, comprises the following steps:

A: l,2-diphenyl-2-methoxyethanol and potassium chloride solution are added to the reaction vessel, the stirring speed is controlled at 230-250 rpm, the temperature of the solution is controlled to 20-26 °C, reacts for 70-90 min, the benzyl salicylate solution is added in batches in 30-50 min, the temperature of the solution is raised to 40-47 °C;

B: cobalt acetylacetonate powder is added, continues to react for 2-3 h, the temperature is reduced to 10-14 °C, the solution layers, washed with sodium sulfate solution for several times, washed with triethylene glycol solution for several times, washed with undecane solution for several times, recrystallizes form the triethylene glycol dimethyl ether solution, dehydrates with dehydration, gets the finished diphenylglycolic acid.

Preferably, the potassium chloride solution has a mass fraction of 5-10%.

Preferably, the mass fraction of the benzyl salicylate solution is 10-16%.

Preferably, the sodium sulfate solution has a mass fraction of 15-22%.

Preferably, the triethylene glycol solution has a mass fraction of 40-46%.

Preferably, the mass fraction of undecane solution is 60-67%.

Preferably, the triethylene glycol dimethyl ether solution has a mass fraction of

80-85%.

Throughout the reaction process can be the following reaction formula:

CH

Compared with the synthesis method disclosed in the background art, the invention provides stomach rehabilitation drug intermediate diphenylglycolic acid synthesis method, it is unnecessary to use nitric acid, sodium hydroxide solution, sulfuric acid solution as reactants, avoiding the corrosion of nitric acid, sodium hydroxide solution, sulfuric acid solution on the equipment, reducing production costs, reducing intermediate links reaction, decreasing the reaction time and improving the reaction yield, at the same time, the present invention provides a new synthetic route which has laid a good foundation for further enhancing the yield of the reaction.

DESCRIPTION OF THE DRAWINGS

Figure 1 shows the ¹³CNMR analysis of finished diphenylglyco lie acid.

Figure 2 is the carbon atom position marker of the diphenylglycolic acid molecule.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

The following examples with reference to specific embodiments of the present invention are further illustrated:

Embodiment 1

Stomach rehabilitation drug intermediate diphenylglycolic acid synthesis method, comprises the following steps:

A: 2 mol l,2-diphenyl-2-methoxyethanol and 1.9L potassium chloride solution with a mass fraction of 5% are added to the reaction vessel, the stirring speed is controlled at 230 rpm, the temperature of the solution is controlled to 20 °C, reacts for 70 min, 4mol benzyl salicylate solution with a mass fraction of 10% is added in batches in 30 min, the temperature of the solution is raised to 40 °C;

B: 2 mol cobalt acetylacetonate powder is added, continues to react for 2 h, the temperature is reduced to 10 °C, the solution layers, washed with sodium sulfate solution with a mass fraction of 15% for 2 times, washed with triethylene glycol solution with a mass fraction of 40% for 3 times, washed with undecane solution with a mass fraction of 60% for 6 times, recrystallizes form the triethylene glycol dimethyl ether solution with a mass fraction of 80%, dehydrates with anhydrous calcium chloride dehydration, gets the finished diphenylglycolic acid 396.72g, yield of 87%.

Embodiment 2

Stomach rehabilitation drug intermediate diphenylglycolic acid synthesis method comprises the following steps:

A: 2 mol l,2-diphenyl-2-methoxyethanol and 1.9L potassium chloride solution with a mass fraction of 7.5% are added to the reaction vessel, the stirring speed is controlled at 240 rpm, the temperature of the solution is controlled to 23 °C, reacts for min, 5mol benzyl salicylate solution with a mass fraction of 13% is added in batches in 40 min, the temperature of the solution is raised to 43.5 °C;

B: 2.5 mol cobalt acetylacetonate powder is added, continues to react for 2.5 h, the temperature is reduced to 12 °C, the solution layers, washed with sodium sulfate solution with a mass fraction of 18.5% for 3 times, washed with triethylene glycol solution with a mass fraction of 43% for 4 times, washed with undecane solution with a mass fraction of 63.5% for 6 times, recrystallizes form the triethylene glycol dimethyl ether solution with a mass fraction of 82.5%, dehydrates with activated alumina dehydration, gets the finished diphenylglycolic acid 419.52g, yield of 92%.

Embodiment 3

A: 2 mol l,2-diphenyl-2-methoxyethanol and 1.9L potassium chloride solution with a mass fraction of 10% are added to the reaction vessel, the stirring speed is controlled at 250 rpm, the temperature of the solution is controlled to 26 °C, reacts for 90 min, 6mol benzyl salicylate solution with a mass fraction of 16% is added in batches in 50 min, the temperature of the solution is raised to 47 °C;

B: 3mol cobalt acetylacetonate powder is added, continues to react for 3h, the temperature is reduced to 14 °C, the solution layers, washed with sodium sulfate solution with a mass fraction of 22% for 4 times, washed with triethylene glycol solution with a mass fraction of 46% for 5 times, washed with undecane solution with a mass fraction of 67% for 7 times, recrystallizes form the triethylene glycol dimethyl ether solution with a mass fraction of 85%, dehydrates with anhydrous calcium chloride dehydration, gets the finished diphenylglycolic acid 437.76g, yield of 96%.

Figure 1 shows the ¹³CNMR analysis of finished diphenylglycolic acid.

Table 1 shows the ¹³CNMR spectra of the finished diphenylglycolic acid.

Table 1 Analysis data chemical shift peak area integration atomic number

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174.61	80	1
143.55	298	2
127.54	915	3*
127.12	484	4
126.99	1000	5*
80.21	144	6

The embodiments of the present invention are merely preferred embodiments of the present invention, but the range of the present invention is not limited this, and any person who is familiar with those skilled in the arts, within the technical range of 10 the present invention. It is intended that the technical solution and its inventive concept be replaced or modified equivalently with reference to the range of the invention.

Claims

Claims

1. Stomach rehabilitation drug intermediate diphenylglycolic acid synthesis method, comprises the following steps:

A: l,2-diphenyl-2-methoxyethanol and potassium chloride solution are added to the reaction vessel, the stirring speed is controlled at 230-250 rpm, the temperature of the solution is controlled to 20-26 °C, reacts for 70-90 min, the benzyl salicylate solution is added in batches in 30-50 min, the temperature of the solution is raised to 40-47 °C;

B: cobalt acetylacetonate powder is added, continues to react for 2-3 h, the temperature is reduced to 10-14 °C, the solution layers, washed with sodium sulfate solution for several times, washed with triethylene glycol solution for several times, washed with undecane solution for several times, recrystallizes form the triethylene glycol dimethyl ether solution, dehydrates with dehydration, gets the finished diphenylglycolic acid.
2. Stomach rehabilitation drug intermediate diphenylglycolic acid synthesis method according to claim 1 wherein the potassium chloride solution has a mass fraction of 5-10%.
3. Stomach rehabilitation drug intermediate diphenylglycolic acid synthesis method according to claim 1 wherein the mass fraction of the benzyl salicylate solution is 10-16%.
4. Stomach rehabilitation drug intermediate diphenylglycolic acid synthesis method according to claim 1 wherein the sodium sulfate solution has a mass fraction of 15-22%.
5. Stomach rehabilitation drug intermediate diphenylglycolic acid synthesis method according to claim 1 wherein the triethylene glycol solution has a mass fraction of 40-46%.

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Figure 2

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