AU2018101116A4 - Vitamin drug intermediates diketone guluronic acid synthesis method - Google Patents
Vitamin drug intermediates diketone guluronic acid synthesis method Download PDFInfo
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- AU2018101116A4 AU2018101116A4 AU2018101116A AU2018101116A AU2018101116A4 AU 2018101116 A4 AU2018101116 A4 AU 2018101116A4 AU 2018101116 A AU2018101116 A AU 2018101116A AU 2018101116 A AU2018101116 A AU 2018101116A AU 2018101116 A4 AU2018101116 A4 AU 2018101116A4
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/12—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains three hetero rings
- C07D493/20—Spiro-condensed systems
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Abstract
Vitamin drug intermediates diketone guluronic acid synthesis method Abstract 5 The present invention discloses vitamin drug intermediates diketone guluronic acid synthesis method, comprises the following steps:2,3,4,6-dione sorbitan methyl ether and butane solution are added to the reaction vessel, raises the temperature of the solution, lead tetraacetate and aqueous solution are added, the stirring speed is controlled, continues to react; then raises the temperature, sodium chloroplatinate 10 powder is added, reacts, oxalic acid solution is added, adjusts the pH, the temperature is lowered, standing, precipitated the solids, washed with potassium chloride solution for, washed with butyl ether solution, and then recrystallizes in 1,4-butanediol solution, dehydrated with dehydration, gets finished product diketone guluronic acid.
Description
The present invention discloses vitamin drug intermediates diketone guluronic acid synthesis method, comprises the following steps:2,3,4,6-dione sorbitan methyl ether and butane solution are added to the reaction vessel, raises the temperature of the solution, lead tetraacetate and aqueous solution are added, the stirring speed is controlled, continues to react; then raises the temperature, sodium chloroplatinate 10 powder is added, reacts, oxalic acid solution is added, adjusts the pH, the temperature is lowered, standing, precipitated the solids, washed with potassium chloride solution for, washed with butyl ether solution, and then recrystallizes in 1,4-butanediol solution, dehydrated with dehydration, gets finished product diketone guluronic acid.
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2018101116 11 Aug2018
Vitamin drug intermediates diketone guluronic 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 vitamin drug intermediates diketone guluronic acid synthesis method.
GENERAL BACKGROUND
Diketone gluconate acid is mainly used for the synthesis of vitamin C drugs.
Most of the existing synthesis methods uses bisketone, sodium hypochlorite, nickel sulfate and hydrochloric acid solution as reactants for the production. This synthesis method requires the use of sodium hypochlorite, hydrochloric acid solution, sodium hypochlorite release free chlorine, which can cause poisoning, it can also cause skin diseases, the solution is corrosive, it can damage the skin, sodium hypochlorite solution and hydrochloric acid solution will corrode the equipment, these factors will increased equipment manufacturing costs, increasing the synthesis process risk factor, which is not conducive to safe production, 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 vitamin drug intermediates diketone guluronic acid synthesis method, comprises the following steps:
A: 2,3,4,6-dione sorbitan methyl ether and butane solution are added to the reaction vessel, raises the temperature of the solution to 40-46 °C, lead tetraacetate and 25 aqueous solution are added, the stirring speed is controlled at 110- 130 rpm, continues to react for 2-3h;
B: then raises the temperature to 50-58 °C, sodium chloroplatinate powder is added, reacts for 60-90 min, oxalic acid solution is added, adjusts the pH to 5-6, the temperature is lowered to 10-14 °C, standing for 30-40 min, precipitated the solids, washed with potassium chloride solution for 40-50 min, washed with butyl ether
2018101116 11 Aug 2018 solution for 20-30 min, and then recrystallizes in 1,4-butanediol solution, dehydrated with dehydration, gets finished product diketone guluronic acid.
Preferably, the butane solution has a mass fraction of 20-26%.
Preferably, the mass fraction of the oxalic acid solution is 25-30%.
Preferably, the potassium chloride solution has a mass fraction of 10-16%.
Preferably, the butyl ether solution has a mass fraction of 70-75%.
Preferably, the mass fraction of 1,4-butanediol solution is 80-86%.
Throughout the reaction process can be the following reaction formula:
CHjOCH,.
Compared with the synthesis method disclosed in the background art, the invention provides vitamin drug intermediates diketone guluronic acid synthesis method, it is unnecessary to use sodium hypochlorite, hydrochloric acid solution as reactants, avoiding the risk ofpoisoning caused by the release of free chlorine, avoiding the corrosion solution damage to skin as well, and corrosivity of sodium hypochlorite 15 solution and hydrochloric acid solution to the device, thus reducing the equipment manufacturing costs, reduce the risk factor during the synthesis process, which is conducive to safe production, 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 20 the yield of the reaction.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
The following examples with reference to specific embodiments of the present invention are further illustrated:
Embodiment 1
Vitamin drug intermediates diketone guluronic acid synthesis method, comprises the following steps:
A: 2 mol 2,3,4,6-dione sorbitan methyl ether and 900ml butane solution with a mass fraction of 20% are added to the reaction vessel, raises the temperature of the solution to 40 °C, 4 mol lead tetraacetate and 4 mol aqueous solution are added, the stirring speed is controlled at HOrpm, continues to react for 2h;
B: then raises the temperature to 50°C, 3 mol sodium chloroplatinate powder is added, reacts for 60 min, oxalic acid solution with a mass fraction of 25% is added, adjusts the pH to 5, the temperature is lowered to 10 °C, standing for 30 min, precipitated the solids, washed with potassium chloride solution with a mass fraction of 10% for 40 min, washed with butyl ether solution with a mass fraction of 70% for 20 min, and then recrystallizes in 1,4-butanediol solution with a mass fraction of 80%, dehydrated with phosphorus pentoxide dehydration, gets finished product diketone guluronic acid 536.172g, yield of 98.2%.
Embodiment 2
Vitamin drug intermediates diketone guluronic acid synthesis method, comprises the following steps:
A: 2 mol 2,3,4,6-dione sorbitan methyl ether and 900ml butane solution with a mass fraction of 23% are added to the reaction vessel, raises the temperature of the solution to 43 °C, 5 mol lead tetraacetate and 5 mol aqueous solution are added, the stirring speed is controlled at 120rpm, continues to react for 2.5h;
B: then raises the temperature to 54°C, 3.5 mol sodium chloroplatinate powder is added, reacts for 75 min, oxalic acid solution with a mass fraction of 27.5% is added, adjusts the pH to 5.5, the temperature is lowered to 12 °C, standing for 35 min, precipitated the solids, washed with potassium chloride solution with a mass fraction of 13% for 45 min, washed with butyl ether solution with a mass fraction of 72.5% for 25 min, and then recrystallizes in 1,4-butanediol solution with a mass fraction of 83%, dehydrated with anhydrous calcium sulphate dehydration, gets finished product diketone guluronic acid 537.8lg, yield of 98.5%.
Embodiment 3
Vitamin drug intermediates diketone guluronic acid synthesis method, comprises the following steps:
2018101116 11 Aug2018
A: 2 mol 2,3,4,6-dione sorbitan methyl ether and 900ml butane solution with a mass fraction of 26% are added to the reaction vessel, raises the temperature of the solution to 46 °C, 6 mol lead tetraacetate and 6 mol aqueous solution are added, the stirring speed is controlled at 130rpm, continues to react for 3h;
B: then raises the temperature to 58°C, 4 mol sodium chloroplatinate powder is added, reacts for 90 min, oxalic acid solution with a mass fraction of 30% is added, adjusts the pH to 6, the temperature is lowered to 14 °C, standing for 40 min, precipitated the solids, washed with potassium chloride solution with a mass fraction of 16% for 50 min, washed with butyl ether solution with a mass fraction of 75% for 30 10 min, and then recrystallizes in 1,4-butanediol solution with a mass fraction of 86%, dehydrated with phosphorus pentoxide dehydration, gets finished product diketone guluronic acid 541.086g, yield of 99.1%.
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 15 any person who is familiar with those skilled in the arts, within the technical range of 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 (5)
- Claims1. Vitamin drug intermediates diketone guluronic acid synthesis method, comprises the following steps:A: 2,3,4,6-dione sorbitan methyl ether and butane solution are added to the reaction vessel, raises the temperature of the solution to 40-46 °C, lead tetraacetate and aqueous solution are added, the stirring speed is controlled at 110-130 rpm, continues to react for 2-3h;B: then raises the temperature to 50-58 °C, sodium chloroplatinate powder is added, reacts for 60-90 min, oxalic acid solution is added, adjusts the pH to 5-6, the temperature is lowered to 10-14 °C, standing for 30-40 min, precipitated the solids, washed with potassium chloride solution for 40-50 min, washed with butyl ether solution for 20-30 min, and then recrystallizes in 1,4-butanediol solution, dehydrated with dehydration, gets finished product diketone guluronic acid.
- 2. Vitamin drug intermediates diketone guluronic acid synthesis method according to claim 1 wherein the butane solution has a mass fraction of 20-26%.
- 3. Vitamin drug intermediates diketone guluronic acid synthesis method according to claim 1 wherein the mass fraction of the oxalic acid solution is 25-30%.
- 4. Vitamin drug intermediates diketone guluronic acid synthesis method according to claim 1 wherein the potassium chloride solution has a mass fraction of 10-16%.
- 5. Vitamin drug intermediates diketone guluronic acid synthesis method according to claim 1 wherein the butyl ether solution has a mass fraction of 70-75%.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710715104.4A CN108239097A (en) | 2017-08-21 | 2017-08-21 | The synthetic method of vitamin drug intermediate diketone golonic acid |
| CN2017107151044 | 2017-08-21 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2018101116A4 true AU2018101116A4 (en) | 2018-09-06 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2018101116A Ceased AU2018101116A4 (en) | 2017-08-21 | 2018-08-11 | Vitamin drug intermediates diketone guluronic acid synthesis method |
Country Status (3)
| Country | Link |
|---|---|
| CN (1) | CN108239097A (en) |
| AU (1) | AU2018101116A4 (en) |
| GB (1) | GB201714080D0 (en) |
-
2017
- 2017-08-21 CN CN201710715104.4A patent/CN108239097A/en active Pending
- 2017-09-04 GB GBGB1714080.7A patent/GB201714080D0/en not_active Ceased
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2018
- 2018-08-11 AU AU2018101116A patent/AU2018101116A4/en not_active Ceased
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| Publication number | Publication date |
|---|---|
| GB201714080D0 (en) | 2017-10-18 |
| CN108239097A (en) | 2018-07-03 |
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