CN103159642A - Preparation method of gliclazide intermediate cyclohexanone-2-methanmide - Google Patents
Preparation method of gliclazide intermediate cyclohexanone-2-methanmide Download PDFInfo
- Publication number
- CN103159642A CN103159642A CN2011104236857A CN201110423685A CN103159642A CN 103159642 A CN103159642 A CN 103159642A CN 2011104236857 A CN2011104236857 A CN 2011104236857A CN 201110423685 A CN201110423685 A CN 201110423685A CN 103159642 A CN103159642 A CN 103159642A
- Authority
- CN
- China
- Prior art keywords
- pimelinketone
- preparation
- water
- methane amide
- cyclohexanone
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of gliclazide intermediate cyclohexanone-2-methanmide. According to the preparation method, spiro-compounds are added in 9.1-9.8% of prepared dilute sulphuric acid, the temperature is raised, and then water and cyclohexanone mixed fraction are obtained. When cyclohexanone does not exist in the fraction, the water is continued to be steamed to be 65-80% of the total water amount, standing and layering are carried out, after a water layer at the bottom is layered, an oil layer at the top is placed into esters solution, the temperature of the solution is raised, backflow is conducted for half an hour, then the temperature of the solution is reduced to be below 10 DEG C and then preserved for 2 hours, and finally white or off-white gliclazide intermediate cyclohexanone-2-methanmide crystalline powder is obtained after suction filtration, washing and drying. According to the preparation method of the gliclazide intermediate cyclohexanone-2-methanmide, synthetic process is easy to operate, reaction conditions are mild, product purity is high, yield coefficients are high, and the preparation method is suitable for commercial process.
Description
Technical field
The present invention relates to the preparation method of a kind of gliclazide intermediate pimelinketone-2-methane amide, belong to technical field of medicine synthesis.
Background technology
Pimelinketone-2-methane amide is the intermediate of synthetic gliclazide, and its chemical equation is as follows:
Gliclazide (gliclazide, GZ) is the oral sulfonylurea hypoglycemic agents of the s-generation, is applicable to the diabetes of non insulin dependent diabetes, obese diabetic, veteran form diabetes and companion's cardiovascular complication.Gliclazide is since French Shi Weiya Developed and after listing in 1972, because its hypoglycemic activity is obvious, can reduce insulin resistant, and few side effects, also can improve microangiopathies, make it become first-selected antidiabetic drug in s-generation sulfonylureas, applying clinical widely.After the introduction of China's later stage 1980s, the market share constantly enlarges, and supply falls short of demand for product.
Pimelinketone-2-methane amide is an important intermediate of synthetic gliclazide, and existing technique synthetic operation is complicated, and yield is low, and is of poor quality.
Summary of the invention
The object of the present invention is to provide the production technique of a kind of pimelinketone-2-methane amide, provide a kind of reaction conditions gentle, be convenient to produce, good product quality, yield is high, the production method of the pimelinketone that cost is low-2-methane amide.
Intermediate methane amide of the present invention improves technique, compares with report technique: the intermediate methane amide steady quality that the method generates, and purity is high, and yield reaches 60%, and is simple to operate, and reaction conditions is gentle, the cheaper suitability for industrialized production of being convenient to of cost.
Technical scheme of the present invention is: add the volution thing in 9.1～9.8% the dilute sulphuric acid for preparing, heat up and steam water and pimelinketone mixed fraction, when there is no pimelinketone in cut, continue to steam water to 65～80% of total Water, standing demix is after telling following water layer, top oil reservoir adds in ethyl acetate, temperature rising reflux half an hour, be cooled to insulation below 10 ℃ 2 hours, crystallization, suction filtration, washing, oven dry gets white or beige pimelinketone-2-methane amide crystalline powder.
Useful benefit of the present invention is: pimelinketone-2-methane amide synthesis technique is simple to operate, and reaction conditions is gentle, and product purity is high, and yield is high, is fit to suitability for industrialized production.
Embodiment
Embodiment
Add volution thing 108g in 9.1～9.8% the dilute sulphuric acid 216g for preparing, heat up and steam water and pimelinketone mixed fraction, when there is no pimelinketone in cut, continue to steam water to 65～80% of total Water, standing demix is after telling following water layer, top oil reservoir adds in the 90g ethyl acetate, temperature rising reflux half an hour, is cooled to insulation below 10 ℃ 2 hours, crystallization, suction filtration, washing, oven dry, get white or beige pimelinketone-2-methane amide crystalline powder 41.5g, yield 60%.
Claims (3)
1. the preparation method of gliclazide intermediate pimelinketone-2-methane amide, it is characterized in that: add volution thing 2.45mol in 9.1～9.8% the dilute sulphuric acid for preparing, intensification steams water and pimelinketone mixed fraction, when there is no pimelinketone in cut, continue to steam water to 65～80% of total Water, standing demix, after telling following water layer, top oil reservoir is put into esters solvent, temperature rising reflux half an hour, is cooled to insulation below 10 ℃ 2 hours, suction filtration, washing, oven dry gets pimelinketone-2-methane amide white or beige crystalline powder.
2. the preparation method of a kind of gliclazide intermediate pimelinketone as claimed in claim 1-2-methane amide is characterized in that: heating up steams water and pimelinketone mixed fraction, when distillating without pimelinketone, continues to steam water to 65～80% of total Water.
3. the preparation method of a kind of gliclazide intermediate pimelinketone as claimed in claim 1-2-methane amide is characterized in that: oil reservoir is refining with esters solvent, and esters solvent comprises ethyl formate, ethyl acetate, methyl acetate, propyl acetate etc.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011104236857A CN103159642A (en) | 2011-12-17 | 2011-12-17 | Preparation method of gliclazide intermediate cyclohexanone-2-methanmide |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011104236857A CN103159642A (en) | 2011-12-17 | 2011-12-17 | Preparation method of gliclazide intermediate cyclohexanone-2-methanmide |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103159642A true CN103159642A (en) | 2013-06-19 |
Family
ID=48583211
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2011104236857A Pending CN103159642A (en) | 2011-12-17 | 2011-12-17 | Preparation method of gliclazide intermediate cyclohexanone-2-methanmide |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103159642A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103664682A (en) * | 2013-11-22 | 2014-03-26 | 中国矿业大学 | Synthetic method for 2-formamide cyclohexanone |
| CN105218394A (en) * | 2015-08-31 | 2016-01-06 | 江苏瑞克医药科技有限公司 | A kind of synthesis technique improving gliclazide intermediate 2-methane amide pimelinketone yield |
| CN112661664A (en) * | 2020-12-30 | 2021-04-16 | 安徽金鼎医药股份有限公司 | Synthesis process of gliclazide intermediate 2-formamide cyclohexanone |
| CN114534644A (en) * | 2022-02-15 | 2022-05-27 | 浙江博朗新材料有限公司 | Device and method for preparing 2-formamide cyclohexanone by catalyzing spiro hydrolysis with solid acid |
-
2011
- 2011-12-17 CN CN2011104236857A patent/CN103159642A/en active Pending
Non-Patent Citations (1)
| Title |
|---|
| 李国防: "2-甲酰胺环己酮的简便合成", 《应用化工》 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103664682A (en) * | 2013-11-22 | 2014-03-26 | 中国矿业大学 | Synthetic method for 2-formamide cyclohexanone |
| CN103664682B (en) * | 2013-11-22 | 2016-01-20 | 中国矿业大学 | A kind of method of synthesizing 2-methane amide pimelinketone |
| CN105218394A (en) * | 2015-08-31 | 2016-01-06 | 江苏瑞克医药科技有限公司 | A kind of synthesis technique improving gliclazide intermediate 2-methane amide pimelinketone yield |
| CN105218394B (en) * | 2015-08-31 | 2017-03-15 | 江苏瑞科医药科技有限公司 | A kind of synthesis technique for improving 2 Methanamide Ketohexamethylene yield of Gliclazide intermediate |
| CN112661664A (en) * | 2020-12-30 | 2021-04-16 | 安徽金鼎医药股份有限公司 | Synthesis process of gliclazide intermediate 2-formamide cyclohexanone |
| CN114534644A (en) * | 2022-02-15 | 2022-05-27 | 浙江博朗新材料有限公司 | Device and method for preparing 2-formamide cyclohexanone by catalyzing spiro hydrolysis with solid acid |
| CN114534644B (en) * | 2022-02-15 | 2023-01-03 | 浙江博朗新材料有限公司 | Device and method for preparing 2-formamide cyclohexanone by catalyzing spiro hydrolysis with solid acid |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103435518B (en) | Preparation method of metformin hydrochloride | |
| CN103159642A (en) | Preparation method of gliclazide intermediate cyclohexanone-2-methanmide | |
| CN105541588B (en) | A kind of synthetic method of diacetyl | |
| CN103159659A (en) | Preparation method of muscarinic receptor antagonist glycopyrronium bromide | |
| CN103420902A (en) | Preparation method of 2-chloro-4-iodo-5-methylpyridine | |
| CN101463011B (en) | Process for synthesizing 3,4-dihydropyrimidine-2-keto | |
| CN103319399B (en) | The preparation method of Egelieting intermediate R-3-amino piperidine dihydrochloride | |
| CN104496937A (en) | Synthetic method of 2-mercaptobenzothiazolyl-(Z)-(2-aminothiazol-4-yl)-2-(tert-butoxycarbonyl) isopropoxyiminoacetate | |
| CN102442944B (en) | Preparation method of flunixin | |
| CN105348069A (en) | Synthesis process of glibenclamide intermediate 5-chlorosalicylic acid | |
| CN102408384A (en) | Improved synthesis method of quinocetone | |
| CN101844992A (en) | Preparation process of Beta lactamine | |
| CN102351699B (en) | Gulonate and preparation method thereof | |
| CN105348101A (en) | Preparation method of methyl p-chlorocinnamate | |
| CN102372687A (en) | Production method for spirodiclofen | |
| CN106045843B (en) | The production technology of racemic ketoprofen isoleucine calcium | |
| CN101709050A (en) | New method for synthesizing 2, 5-dichloropyridine | |
| CN102432524A (en) | Method for preparing indole-2-carboxylic acid | |
| CN101823986A (en) | Preparation method for tert-butyl carbazate | |
| CN102633624B (en) | Method for preparing methylcinnamic acid | |
| CN103772284B (en) | A kind of preparation method of 4,5-diaminostilbene-(2-hydroxyethyl) pyrazoles vitriol | |
| CN103183632A (en) | Purification method of 3-azabicyclo-octane hydrochloride | |
| CN102476981A (en) | Method for preparing 1,3,5-trimethoxybenzene | |
| CN104529798B (en) | A kind of preparation method of Etoricoxib intermediate 3-amino-2-chloroacrolein | |
| CN102731384B (en) | A kind of synthetic method of the 6-methylnicotinic acid tert-butyl ester |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20130619 |