IES87060B2 - Butyraldehyde oxime drug itermediates synthesis method - Google Patents
Butyraldehyde oxime drug itermediates synthesis method Download PDFInfo
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- IES87060B2 IES87060B2 IES20180250A IES87060B2 IE S87060 B2 IES87060 B2 IE S87060B2 IE S20180250 A IES20180250 A IE S20180250A IE S87060 B2 IES87060 B2 IE S87060B2
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- butyraldehyde oxime
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- DMJZWFZICOEEAJ-UHFFFAOYSA-N 2-(4-bromothiophen-3-yl)sulfanylpropanoic acid Chemical compound OC(=O)C(C)SC1=CSC=C1Br DMJZWFZICOEEAJ-UHFFFAOYSA-N 0.000 title claims abstract description 22
- 238000001308 synthesis method Methods 0.000 title claims abstract description 17
- 239000003814 drug Substances 0.000 title claims abstract description 15
- 229940079593 drug Drugs 0.000 title claims abstract description 15
- 239000000243 solution Substances 0.000 claims abstract description 52
- 239000000543 intermediate Substances 0.000 claims abstract description 17
- 238000006243 chemical reaction Methods 0.000 claims abstract description 16
- FJKIXWOMBXYWOQ-UHFFFAOYSA-N ethenoxyethane Chemical compound CCOC=C FJKIXWOMBXYWOQ-UHFFFAOYSA-N 0.000 claims abstract description 16
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 claims abstract description 16
- WMIYKQLTONQJES-UHFFFAOYSA-N hexafluoroethane Chemical compound FC(F)(F)C(F)(F)F WMIYKQLTONQJES-UHFFFAOYSA-N 0.000 claims abstract description 8
- OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 claims abstract description 7
- 229910052939 potassium sulfate Inorganic materials 0.000 claims abstract description 7
- 235000011151 potassium sulphates Nutrition 0.000 claims abstract description 7
- VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical compound CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000007864 aqueous solution Substances 0.000 claims abstract description 6
- -1 bromosuccinic acid imide Chemical class 0.000 claims abstract description 6
- WYYQVWLEPYFFLP-UHFFFAOYSA-K chromium(3+);triacetate Chemical compound [Cr+3].CC([O-])=O.CC([O-])=O.CC([O-])=O WYYQVWLEPYFFLP-UHFFFAOYSA-K 0.000 claims abstract description 6
- 230000018044 dehydration Effects 0.000 claims abstract description 6
- 238000006297 dehydration reaction Methods 0.000 claims abstract description 6
- 239000000843 powder Substances 0.000 claims abstract description 6
- 238000003756 stirring Methods 0.000 claims abstract description 6
- OWXJKYNZGFSVRC-NSCUHMNNSA-N (e)-1-chloroprop-1-ene Chemical compound C\C=C\Cl OWXJKYNZGFSVRC-NSCUHMNNSA-N 0.000 claims abstract description 5
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 16
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 5
- 229940095564 anhydrous calcium sulfate Drugs 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000004880 explosion Methods 0.000 description 3
- 239000002360 explosive Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000007800 oxidant agent Substances 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 206010008479 Chest Pain Diseases 0.000 description 2
- 206010013975 Dyspnoeas Diseases 0.000 description 2
- 230000007794 irritation Effects 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 208000004998 Abdominal Pain Diseases 0.000 description 1
- 206010010071 Coma Diseases 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 206010037423 Pulmonary oedema Diseases 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 238000002485 combustion reaction Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000000383 hazardous chemical Substances 0.000 description 1
- 231100000206 health hazard Toxicity 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000012450 pharmaceutical intermediate Substances 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 208000005333 pulmonary edema Diseases 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- XMVONEAAOPAGAO-UHFFFAOYSA-N sodium tungstate Chemical compound [Na+].[Na+].[O-][W]([O-])(=O)=O XMVONEAAOPAGAO-UHFFFAOYSA-N 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention discloses drug intermediates butyraldehyde oxime drug intermediates synthesis method, comprises the following steps: 1-chlorobutane and potassium sulfate solution were added to the reaction vessel, raised the temperature of the solution, controlled the stirring speed, added aqueous solution and ethyl vinyl ether solution, added bromosuccinic acid imide in batches, continued to react; then added chromium acetate powder, raised the temperature of the solution, continued to react, washed with potassium bromide solution, washed with hexafluoroethane solution, recrystallized in chloropropene solution, dehydrated with dehydration, got the finished product butyraldehyde oxime.
Description
Butyraldehyde oxime drag intermediates synthesis method
FIELD OF THE INVENTION
I he present invention relates to a method for preparing a pharmaceutical intermediate which belongs to the field of organic synthesis, more particularly, relates to drug intermediates butyraldehyde oxime drug intermediates synthesis method.
GENERAL BACKGROUND
Butyraldehyde oxime is mainly used as an intermediate for pharmaceutical synthesis and can also be used in other organic synthesis. Most of the existing synthesis methods use butylamine, sodium tungstate and hydrogen peroxide as reaction raw materials to compoud butyraldehyde oxime. In synthetic method, the reaction material butylamine is flammable, its vapor and air can form an explosive mixture. When meeting open fire, high heat, it can cause combustion explosion. It can react strongly with the oxidant. Its vapor is heavier than air, and can spread at a lower place to a considerable distance, when meeting a fire source will lead back to the fire. When meeting high heat, the container pressure increases, and there will be the ri.sk of crackmg and explosion. Butylamine is corrosive. Butylamine has a strong irritation io the lespiratory tract, after inhalation can cause cough, difficulty breathing, chest pain, pulmonary edema and coma; Butylamine has a strong irritation to the eyes and skin and can even cause burns. These factors indicate that butylamine as a reactive material, not only will lead to increase risk factor of the reaction process, but also will endanger the health of the production operators. Reaction raw7 material hydrogen peroxide is an explosive strong oxidizing agent. In a. sealed container with an appropriate ignition source or temperature, it will cause gas explosion. It has a strong corrosive. Inhalation of its steam or fog will irritate the respiratory tract strongly. Poisoning will be abdominal pain, chest pain, difficulty breathing, vomiting, temporary exercise and sensoiy disturbances, elevated body temperature and so on. Therefore, hydrogen peioxide as a ieaction raw material is not conducive to safety production, and also endangeis the health of production operators. The analysis of these factors show's that theie are many shortcomings in this synthetic method, so it. is necessary to propose a new synthesis method.
SUMMARY
Based on the technical problems of the background technology, the purpose of the pi esent invention is to provide butyraldehyde oxime drug intermediates synthesis method, comprises the following steps:
A. 1 -chlorobutane and potassium sulfate solution were added to the reaction vessel, laised the temperature ofthe solution to 20-27 ‘C, controlled the stirring speed at 350-380 rpm, added aqueous solution and ethyl vinyl ether solution, in 30-50 min, added bromosuccinic acid imide in batches, continued to react for 90-120 min;
B. then added chromium acetate powder, raised the temperature of the solution to 30-36 C, continued to react for 2-3 h, washed with potassium bromide solution for 30-40 min, washed with hexafluoroethane solution for 50-70 min, recrystallized in chloi opropene solution, dehydrated with dehydration, got the finished product butyraldehyde oxime.
Preferably, potassium sulfate solution has a mass fraction of 10-16%.
Preferably, ethyl vinyl ether solution has mass fraction of20-25%».
Preferably, potassium bromide solution has mass fraction of 15-22%.
Preferably, hexafluoroethane solution has mass fraction of 30-36%.
Preferably, chloropropene solution has a mass fraction of 60-65%.
Ihioughout the reaction process can be the following reaction formula:
CIJ3CH2CH2CH2 + C5H8O + C4H4BrN(% + C6H$OsCr + h,o _____, ΐ - - ”
Cl
Compared with the synthesis method disclosed in the background art, the invention provides butyraldehyde oxime drug intermediates synthesis method, it is unnecessary to use butylamine and hydrogen peroxide as the reaction of raw materials, avoids the flammable and corrosive butylamine, which will lead to the risk in the synthesis process and the health hazards of the production operators. It also avoids the adverse effects of explosive oxygen oxidant hydrogen peroxide on production safety, reducing the risk factor of the synthesis process, which is conducive to safety production. It also reduces intermediate links reaction, decreases the reaction time and improves 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.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
The following examples with reference to specific embodiments of the present invention are further illustrated:
Embodiment 1
Butyraldehyde oxime drug intermediates synthesis method, comprises the following steps:
A: 3mol 1-chlorobutane and 900 ml potassium sulfate solution with a mass fraction of 10% were added to the reaction vessel, raised the temperature of the solution to 20 °C, controlled the stirring speed at 350 rpm, added 6mol aqueous solution and 6 mol ethyl vinyl ether solution with a mass fraction of 20%, in 30 min. added 6mol bromosuccinic acid imide in 2 times, continued to react for 90 min;
B: then added 3mol chromium acetate powder, raised the temperature of the solution to 30 JC, continued to react for 2 h, washed with potassium bromide solution with a mass fraction of 15% for 30 min, washed with hexafluoroethane solution with a mass fraction of 30% for 50 min, recrystallized in chloropropene solution with a mass fraction of 60%, dehydrated with anhydrous calcium sulfate dehydration, got the finished product butyraldehyde oxime 254.997g, yield of 97.7%.
Embodiment 2
Butyraldehyde oxime drug intermediates synthesis method, comprises the following steps:
A: 3mol 1-chlorobutane and 900 ml potassium sulfate solution with a mass fraction of 13% were added to the reaction vessel, raised the temperature of the solution to 24 C, controlled the stirring speed at j60 rpm, added 7moi aqueous solution and 7mol ethyl vinyl ether solution with a mass fraction of z.3 /o, in 40 min, added 7mol bromosuccinic acid imide in 3 times, continued to react foj 100 min,
B: then added 4mol chromium acetate powder, raised the temperature of the solution to 33 °C, continued to react for 2.5 h, washed with potassium bromide solution with a mass fraction of 18% for 35 min, washed with hexafluoroethane solution with a mass fraction of 33% for 60 min, recrystallized in chloropiopene solution with a mass fraction of 63%, dehydrated with anhydrous calcium sulfate dehydration, got the finished product butyraldehyde oxime 2o5.519g, yield of 97.9%.
Embodiment 3
Butyraldehyde oxime drug intermediates synthesis method, comprises the following steps:
A: 3mol 1 -chlorobutane and 900 ml potassium sulfate- solution with a mass fraction of 16% were added to the reaction vessel, raised the temperature of the solution to 27 °C, controlled the stirring speed at 380 rpm, added 8 mol aqueous solution and 8mol ethyl vinyl ether solution with a mass fraction of 25%, in 50 min, added 8mol bromosuccinic acid imide in 4times, continued to react, for 120 min,
B: then added 5 mol chromium acetate powder, raised the temperature of the solution to 36 °C, continued to react for 3 h, washed with potassium bromide solution with a mass fraction of 22% for 40 min, washed with hexafluoroethane solution with a mass fraction of 36% for 70 min, recrystallized in chloropropene solution with a mass fraction of 65%, dehydrated with anhydrous calcium sulfate dehydration, got the finished product butyraldehyde oxime 256.302g, yield of 98.2%.
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 the present Invention. It is intended that the technical solution and its inventive concept be replaced or modified equivalently with reference to the iange of the invention.
Claims (5)
1. Butyraldehyde oxime drug intermediates synthesis method, comprises the following steps: 5 A: 1-chlorobutane and potassium sulfate solution were added to the reaction vessel, raised the temperature of the solution to 20-27 °C, controlled the stirring speed at 350-380 rpm, added aqueous solution and ethyl vinyl ether solution, in 30-50 min, added bromosuccinic acid imide in batches, continued to react for 90-120 min; B: then added chromium acetate powder, raised the temperature of the solution to 10 30-36 C, continued to react for 2-3 h, washed with potassium bromide solution for 30-40 min, washed with hexafluoroethane solution for 50-70 min, recrystallized in chloropropene solution, dehydrated with dehydration, got the finished product butyraldehyde oxime.
2. Butyraldehyde oxime drug intermediates synthesis method according to claim 15 1 wherein potassium sulfate solution has a mass fraction of 10-16%.
3. Butyraldehyde oxime drug intermediates synthesis method according to claim 1 wherein ethyl vinyl ether solution lias mass fraction of 20-25%,
4. Butyraldehyde oxime drug intermediates synthesis method according to claim 1 wherein potassium bromide solution has mass fraction of 15-22%. 20
5. Butyraldehyde oxime drug intermediates synthesis method according to claim 1 wherein hexafluoroethane solution has mass fraction of30-36%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IES20180250 IES87060B2 (en) | 2018-08-16 | 2018-08-16 | Butyraldehyde oxime drug itermediates synthesis method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IES20180250 IES87060B2 (en) | 2018-08-16 | 2018-08-16 | Butyraldehyde oxime drug itermediates synthesis method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IES20180250A2 IES20180250A2 (en) | 2019-10-30 |
| IES87060B2 true IES87060B2 (en) | 2019-10-30 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IES20180250 IES87060B2 (en) | 2018-08-16 | 2018-08-16 | Butyraldehyde oxime drug itermediates synthesis method |
Country Status (1)
| Country | Link |
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| IE (1) | IES87060B2 (en) |
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2018
- 2018-08-16 IE IES20180250 patent/IES87060B2/en unknown
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| Publication number | Publication date |
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| IES20180250A2 (en) | 2019-10-30 |
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