IES86991B2 - Drug intermediates isovaleric acid synthesis method - Google Patents
Drug intermediates isovaleric acid synthesis method Download PDFInfo
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- IES86991B2 IES86991B2 IES20180086A IES20180086A IES86991B2 IE S86991 B2 IES86991 B2 IE S86991B2 IE S20180086 A IES20180086 A IE S20180086A IE S20180086 A IES20180086 A IE S20180086A IE S86991 B2 IES86991 B2 IE S86991B2
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- solution
- added
- mass fraction
- isovaleric acid
- mol
- Prior art date
Links
- GWYFCOCPABKNJV-UHFFFAOYSA-N beta-methyl-butyric acid Natural products CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 title claims abstract description 20
- GWYFCOCPABKNJV-UHFFFAOYSA-M 3-Methylbutanoic acid Natural products CC(C)CC([O-])=O GWYFCOCPABKNJV-UHFFFAOYSA-M 0.000 title claims abstract description 18
- XYHKNCXZYYTLRG-UHFFFAOYSA-N 1h-imidazole-2-carbaldehyde Chemical compound O=CC1=NC=CN1 XYHKNCXZYYTLRG-UHFFFAOYSA-N 0.000 title claims abstract description 16
- 239000000543 intermediate Substances 0.000 title claims abstract description 10
- 238000001308 synthesis method Methods 0.000 title claims abstract description 9
- 239000003814 drug Substances 0.000 title claims abstract description 8
- 229940079593 drug Drugs 0.000 title claims abstract description 8
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims abstract description 16
- 238000006243 chemical reaction Methods 0.000 claims abstract description 10
- SBASXUCJHJRPEV-UHFFFAOYSA-N 2-(2-methoxyethoxy)ethanol Chemical compound COCCOCCO SBASXUCJHJRPEV-UHFFFAOYSA-N 0.000 claims abstract description 8
- IEJIGPNLZYLLBP-UHFFFAOYSA-N dimethyl carbonate Chemical compound COC(=O)OC IEJIGPNLZYLLBP-UHFFFAOYSA-N 0.000 claims abstract description 8
- HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical compound CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 claims abstract description 8
- 229910000343 potassium bisulfate Inorganic materials 0.000 claims abstract description 8
- 239000001103 potassium chloride Substances 0.000 claims abstract description 8
- 235000011164 potassium chloride Nutrition 0.000 claims abstract description 8
- 229910021380 Manganese Chloride Inorganic materials 0.000 claims abstract description 6
- GLFNIEUTAYBVOC-UHFFFAOYSA-L Manganese chloride Chemical compound Cl[Mn]Cl GLFNIEUTAYBVOC-UHFFFAOYSA-L 0.000 claims abstract description 6
- 239000012024 dehydrating agents Substances 0.000 claims abstract description 6
- 239000011565 manganese chloride Substances 0.000 claims abstract description 6
- 235000002867 manganese chloride Nutrition 0.000 claims abstract description 6
- 229940099607 manganese chloride Drugs 0.000 claims abstract description 6
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 claims abstract description 6
- 238000003756 stirring Methods 0.000 claims abstract description 6
- CAWHJQAVHZEVTJ-UHFFFAOYSA-N methylpyrazine Chemical compound CC1=CN=CC=N1 CAWHJQAVHZEVTJ-UHFFFAOYSA-N 0.000 claims description 4
- JTNCEQNHURODLX-UHFFFAOYSA-N 2-phenylethanimidamide Chemical compound NC(=N)CC1=CC=CC=C1 JTNCEQNHURODLX-UHFFFAOYSA-N 0.000 claims description 2
- QVMRSFQXWJGXRL-UHFFFAOYSA-N 1-chloro-4-methylpentan-2-one Chemical compound CC(C)CC(=O)CCl QVMRSFQXWJGXRL-UHFFFAOYSA-N 0.000 abstract description 2
- 239000000047 product Substances 0.000 description 5
- 235000013599 spices Nutrition 0.000 description 3
- HVJKZICIMIWFCP-UHFFFAOYSA-N Benzyl 3-methylbutanoate Chemical compound CC(C)CC(=O)OCC1=CC=CC=C1 HVJKZICIMIWFCP-UHFFFAOYSA-N 0.000 description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
- XINCECQTMHSORG-UHFFFAOYSA-N Isoamyl isovalerate Chemical compound CC(C)CCOC(=O)CC(C)C XINCECQTMHSORG-UHFFFAOYSA-N 0.000 description 2
- PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- QDLAABKFYZVHOW-UHFFFAOYSA-N 2-bromo-3-iodonaphthalene Chemical compound C1=CC=C2C=C(I)C(Br)=CC2=C1 QDLAABKFYZVHOW-UHFFFAOYSA-N 0.000 description 1
- FOCMOGKCPPTERB-UHFFFAOYSA-N Isovaleriansaeure-trans-cinnamylester Natural products CC(C)CC(=O)OCC=CC1=CC=CC=C1 FOCMOGKCPPTERB-UHFFFAOYSA-N 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- 235000013832 Valeriana officinalis Nutrition 0.000 description 1
- 244000126014 Valeriana officinalis Species 0.000 description 1
- 244000290333 Vanilla fragrans Species 0.000 description 1
- 235000009499 Vanilla fragrans Nutrition 0.000 description 1
- 235000012036 Vanilla tahitensis Nutrition 0.000 description 1
- FOCMOGKCPPTERB-RMKNXTFCSA-N [(e)-3-phenylprop-2-enyl] 3-methylbutanoate Chemical compound CC(C)CC(=O)OC\C=C\C1=CC=CC=C1 FOCMOGKCPPTERB-RMKNXTFCSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 235000013351 cheese Nutrition 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000008369 fruit flavor Substances 0.000 description 1
- 239000000175 humulus lupulus l. cone oil Substances 0.000 description 1
- -1 isovalerate hexahydrate Chemical compound 0.000 description 1
- 239000001683 mentha spicata herb oil Substances 0.000 description 1
- VKULUTKCTSMXPO-UHFFFAOYSA-N neryl isovalerate Natural products CC(C)CC(=O)OCC(=CCCC=C(C)C)C VKULUTKCTSMXPO-UHFFFAOYSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 239000001920 pimenta acris kostel leaf oil terpeneless Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000004799 sedative–hypnotic effect Effects 0.000 description 1
- 235000019721 spearmint oil Nutrition 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 235000016788 valerian Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Hydrogenated Pyridines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Drug intermediates isovaleric acid synthesis method, comprises the following steps: 2 mol 1-chloro-3-isopropylacetone and 4-5 mol dimethyl carbonate solution were added to the reaction vessel, control the stirring speed at 110-140 rpm, the solution temperature was raised to 30-40 t, and then added 3-4 mol manganese chloride, reacted for 70-90 min, added 900 ml potassium chloride solution, reduced the temperature of the solution to 20-25 °C, added potassium hydrogen sulfate solution to adjust the pH to 4-5, standing for 50-70 mm, the solution was layered, washed with a methyl carbitol solution, washed with a methyl hydrazine solution, recrystallized from 1-methylpiazepine solution, and dehydrated with the dehydrating agent, finally obtained the product isovaleric acid.
Description
Drag intermediates isovaleric acid synthesis method
FIELD OF THE INVENTION
The present invention relates to drug intermediates isovaleric acid synthesis method.
GENERAL BACKGROUND
Isovaleric acid is used for the production of sedative hypnotics bromoisovaleride, but more for the production of spices, the isovalerate used as a perfume mainly includes isovalerate hexahydrate, isovalerate, isopentyl isovalerate, geranyl isovalerate, benzyl isovalerate and cinnamyl isovalerate. Lower isovalerate esters is used for edible spices, and higher isovalerate esters for cosmetics. Isovalic acid natural stored in valerian oil, vanilla oil, hops oil, bay leaf oil, spearmint oil, etc., the Chinese national standard GB2760-86 provides for the use of food spices, mainly for the preparation of cheese and cream flavor, but also trace for fruit flavor. However, most of the existing synthetic methods are using isoamyl alcohol oxidation synthesis, it is complicated and the final yield is not very high. Therefore, it is necessary to propose a new synthetic method for further improving the quality and yield of the product and reducing the byproduct content, it has important economic significance.
SUMMARY
The purpose of the present invention is to provide drug intermediates isovaleric acid synthesis method, comprises the following steps:
(i) 2 mol l-chloro-3-isopropylacetone and 4-5 mol dimethyl carbonate solution were added to the reaction vessel, control the stirring speed at 110-140 rpm, the solution temperature was raised to 30-40 °C, and then added 3-4 mol manganese chloride, reacted for 70-90 min, added 900 ml potassium chloride solution, reduced the temperature of the solution to 20-25 °C, added potassium hydrogen sulfate solution to adjust the pH to 4-5, standing for 50-70 min, the solution was layered, washed with a methyl carbitol solution, washed with a methyl hydrazine solution, recrystallized from
I -methyIpiazepine solution, and dehydrated with the dehydrating agent, finally obtained the product isovaleric acid; wherein, the mass fraction of the dimethyl carbonate solution in step (i) is 70 to 76%, the mass fraction of the potassium chloride solution in step (i) is 10 to 16%, the mass fraction of the potassium bisulfate solution described in step (i) is 20 to 25% , the mass fraction of the methyl carbitol solution in step (i) is 60 to 68%, the mass fraction of the methylhydrazine solution in step (i) is 80 to 87%, the 1 - the methylpyrazine solution has a mass fraction of 90-95%.
Throughout the reaction process can be the following reaction formula:
h3c. ch3
-V
Cl I
MnCk
CH
I , OH
Advantage of the present invention is that: reducing intermediate links reaction, decreasing the reaction time and improving the reaction yield.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
The following examples with reference to specific embodiments of the present invention are further illustrated:
drug intermediates isovaleric acid synthesis method.
Embodiment 1 mol l-chloro-3-isopropylacetone and 4mol dimethyl carbonate solution with a mass fraction of 70%, were added to the reaction vessel, controlled the stirring speed at 110 rpm, the solution temperature was raised to 30 “C, and then added 3 mol manganese chloride, reacted for 70 min, added 900 ml potassium chloride solution with a mass fraction of 10%, reduced the temperature of the solution to 20 °C, added potassium hydrogen sulfate solution with a mass fraction of 20% to adjust the pH to 4, standing for 50 min, the solution was layered, washed with a methyl carbitol solution with a mass fraction of 60%„ washed with a methyl hydrazine solution with a mass fraction of 80%, recrystallized from 1 -methylpiazepine solution with a mass fraction of
90%, and dehydrated with the anhydrous calcium chloride dehydrating agent, finally obtained the product isovaleric acid 181.56 g, yield of 89%.
Embodiment 2 mol 1 -chloro-3-isopropylacetone and 4.5mol dimethyl carbonate solution with a mass fraction of 73%, were added to the reaction vessel, controlled the stirring speed at 120 rpm, the solution temperature was raised to 35 °C, and then added 3.5 mol manganese chloride, reacted for 80 min, added 900 ml potassium chloride solution with a mass fraction of 13%, reduced the temperature of the solution to 23 °C, added potassium hydrogen sulfate solution with a mass fraction of 23% to adjust the pH to 4.5, standing for 60 mm, the solution was layered, washed with a methyl carbitol solution with a mass fraction of 64%,, washed with a methyl hydrazine solution with a mass fraction of 83%, recrystallized from 1 -methylpiazepine solution with a mass fraction of 92%, and dehydrated with the anhydrous magnesium sulfate dehydrating agent, finally obtained the product isovaleric acid 187.68 g, yield of 92%.
Embodiment 3 mol l-chloro-3-isopropylacetone and 5mol dimethyl carbonate solution with a mass fraction of 76%, were added to the reaction vessel, controlled the stirring speed at 140 rpm, the solution temperature was raised to 40 °C, and then added 4 mol manganese chloride, reacted for 90 min, added 900 ml potassium chloride solution with a mass fraction of 16%, reduced the temperature of the solution to 25 °C, added potassium hydrogen sulfate solution with a mass fraction of 25% to adjust the pH to 5, standing for 70 min, the solution was layered, washed with a methyl carbitol solution with a mass fraction of 65%,, washed with a methyl hydrazine solution with a mass fraction of 87%, recrystallized from 1-methylpiazepine solution with a mass fraction of 95%, and dehydrated with the anhydrous calcium chloride dehydrating agent, finally obtained the product isovaleric acid 191.76 g, yield of 94%.
Claims (3)
1. Drug intermediates isovaleric acid synthesis method, comprises the following steps: (i) 2 mol l-chloro-3-isopropylacetone and 4-5 mol dimethyl carbonate solution were added to the reaction vessel, control the stirring speed at 110-140 rpm, the solution temperature was raised to 30-40 °C, and then added 3-4 mol manganese chloride, reacted for 70-90 min, added 900 ml potassium chloride solution, reduced the temperature of the solution to 20-25 °C, added potassium hydrogen sulfate solution to adjust the pH to 4-5, standing for 50-70 min, the solution was layered, washed with a methyl carbitol solution, washed with a methyl hydrazine solution, recrystallized from 1 -methylpiazepine solution, and dehydrated with the dehydrating agent, finally obtained the product isovaleric acid; wherein, the mass fraction of the dimethyl carbonate solution in step (i) is 70 to 76%, the mass fraction of the potassium chloride solution in step (i) is 10 to 16%, the mass fraction ofthe potassium bisulfate solution described in step (i) is 20 to 25% , the mass fraction ofthe methyl carbitol solution in step (i) is 60 to 68%.
2. Drug intermediates isovaleric acid synthesis method according to claim 1 wherein the mass fraction of the methylhydrazine solution in step (i) is 80 to 87%.
3. Drug intermediates isovaleric acid synthesis method according to claim 1 wherein the 1- the methylpyrazine solution has a mass fraction of 90-95%.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710216243.2A CN108238893A (en) | 2017-04-05 | 2017-04-05 | A kind of synthetic method of pharmaceutical intermediate isovaleric acid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IES20180086A2 IES20180086A2 (en) | 2019-04-03 |
| IES86991B2 true IES86991B2 (en) | 2019-05-01 |
Family
ID=59220686
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IES20180086A IES86991B2 (en) | 2017-04-05 | 2018-04-03 | Drug intermediates isovaleric acid synthesis method |
Country Status (4)
| Country | Link |
|---|---|
| CN (1) | CN108238893A (en) |
| AU (1) | AU2018100421A4 (en) |
| GB (1) | GB201708117D0 (en) |
| IE (1) | IES86991B2 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110776412B (en) * | 2019-11-12 | 2022-04-22 | 万华化学集团股份有限公司 | Method for preparing isovaleric acid, ligand, complex and application thereof in catalytic system |
-
2017
- 2017-04-05 CN CN201710216243.2A patent/CN108238893A/en active Pending
- 2017-05-22 GB GBGB1708117.5A patent/GB201708117D0/en not_active Ceased
-
2018
- 2018-04-01 AU AU2018100421A patent/AU2018100421A4/en not_active Ceased
- 2018-04-03 IE IES20180086A patent/IES86991B2/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AU2018100421A4 (en) | 2018-05-10 |
| IES20180086A2 (en) | 2019-04-03 |
| GB201708117D0 (en) | 2017-07-05 |
| CN108238893A (en) | 2018-07-03 |
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