CN101117331A - Method for preparing 3-pyridine acetic acid hydrochloride - Google Patents
Method for preparing 3-pyridine acetic acid hydrochloride Download PDFInfo
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- CN101117331A CN101117331A CNA200610069863XA CN200610069863A CN101117331A CN 101117331 A CN101117331 A CN 101117331A CN A200610069863X A CNA200610069863X A CN A200610069863XA CN 200610069863 A CN200610069863 A CN 200610069863A CN 101117331 A CN101117331 A CN 101117331A
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- acid hydrochloride
- pyridine
- morpholine
- morphine quinoline
- thioacetyl
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Abstract
The invention discloses a preparation process for 3-Pyridylacetic acid hydrochloride. The 3-vinylpyridine is taken as the raw material, is reacted with the morpholine and the sulphur, and then is poured into the ice water to be filtered; the crystal is washed by ice water and is naturally dried in the air to produce the 3-pyridyi thio aeid morpholine; the 3-pyridyi thio aeid morpholine is hydrolyzed by the hydrochloric acid, after the dehydration, the 3-pyridyi thio aeid morpholine is decolored by the activated carbon, is made a pressure reduction concentration, is cooled and made a crystal precipitation to produce the 3-Pyridylacetic acid hydrochloride. The invention directly takes 3-vinylpyridine as the raw material, produces the 3-Pyridylacetic acid hydrochloride only by two steps chemical reactions, develops a new path for the preparation of 3-Pyridylacetic acid hydrochloride; moreover, the preparation process is greatly shortened, the operation is simple, the yields are above 86 percent, and the quality of the product is apparently improved.
Description
Technical field
The present invention relates to the synthetic method of pharmaceutical intermediate 3-Pyridineacetic Acid hydrochloride.
Background technology
The 3-Pyridineacetic Acid hydrochloride, its chemical structural formula is:
It is key intermediate for synthetic anti-osteoporotic risedronate sodium (Risedronate sodium).Osteoporosis is a kind of general metabolism disease, with the microstructure degeneration of the minimizing of bone amount, bone, the fragility increase and the easy fracture of bone is feature, become the elderly, especially postmenopausal women's common disease, frequently-occurring disease, once being called by the western medicine expert is " 21st century is endangered one of three maximum big diseases to the mankind ".Risedronate sodium is a third generation bisphosphonates bone resorption inhibitor, is applicable to post-menopausal osteoporosis and the osteoporosis because of using cortin to cause, the osteoporosis that also can prevent high risk population among the women.Its safety, effective, better tolerance, application prospect is good.
Chinese Journal of Pharmaceuticals (2003,33 (9): 427) disclose a kind of method for preparing the 3-Pyridineacetic Acid hydrochloride: with the Nikithan is raw material, through lithium aluminium hydride reduction, thionyl chloride chlorination, potassium cyanide replacement, hydrolysis and must the 3-Pyridineacetic Acid hydrochloride.This method is used valuable raw material lithium aluminium hydride and violent in toxicity potassium cyanide, and total recovery is lower, the cost height.
Also have, J Am Chem Soc.1957,79:4226 and J Am Chem Soc, 1947,69 (7): 1797 also disclose a kind of preparation method of 3-Pyridineacetic Acid hydrochloride: be raw material with the Nikithan, get 3-acetylpyridine through condensation and hydrolysis, again through the Willgerodt of improvement reaction, obtain 3-pyridine thioacetyl morphine quinoline, after hydrolysis gets the 3-Pyridineacetic Acid hydrochloride.This law total recovery is higher, and cost is lower.But the first step reaction needs with sodium hydride and sodium methylate (or sodium ethylate) in this law, yield 81-85%, and the sodium hydride price is more expensive, and sodium methylate (or sodium ethylate) is difficult for preserving.Basic hydrolysis is used in final step, the aftertreatment more complicated, and sodium-chlor is difficult to eliminate, yield 74%, mp153-155 ℃.
In addition, Chinese invention patent application CN1431198A also discloses a kind of preparation method of 3-Pyridineacetic Acid hydrochloride, substituted catalyzer sodium methylate (or sodium ethylate) in the above-mentioned second method with sodium Metal 99.5 in this method, changed hydrolysising condition, the shortcoming of this method is that sodium Metal 99.5 has certain danger aborning.
Summary of the invention
Technical problem to be solved by this invention is: a kind of method for preparing the 3-Pyridineacetic Acid hydrochloride is provided, and this method steps is simple, the yield height, and quality product obviously improves.
For solving the problems of the technologies described above, technical scheme of the present invention is: prepare the method for 3-Pyridineacetic Acid hydrochloride, may further comprise the steps:
With the 3-vinyl pyridine is raw material, after finishing with morphine quinoline and sulfur reaction, pours in the frozen water and filters, and crystal washs with frozen water, and seasoning in air makes 3-pyridine thioacetyl morphine quinoline;
3-pyridine thioacetyl morphine quinoline is hydrolyzed with hydrochloric acid, after hydrolysis finishes, through activated carbon decolorizing, concentrating under reduced pressure, cooling crystallization makes the 3-Pyridineacetic Acid hydrochloride.
In conjunction with chemical equation, the preparation method is as follows more specifically:
A) preparation process of 3-pyridine thioacetyl morphine quinoline
3-vinyl pyridine 3-pyridine thioacetyl morphine quinoline
In the presence of sulphur, 3-vinyl pyridine and the reaction of morphine quinoline, reaction is finished, and pours in the frozen water and filters, and crystal washs with frozen water, and seasoning promptly gets 3-pyridine thioacetyl morphine quinoline in the air;
B) preparation process of 3-Pyridineacetic Acid hydrochloride
3-pyridine thioacetyl morphine quinoline 3-Pyridineacetic Acid hydrochloride
3-pyridine thioacetyl morphine quinoline is hydrolyzed with hydrochloric acid, and hydrolysis finishes, behind activated carbon decolorizing, and concentrating under reduced pressure, cooling crystallization, refining pure 3-Pyridineacetic Acid hydrochloride.
Because the present invention is a raw material with the 3-vinyl pyridine directly, just can make the 3-Pyridineacetic Acid hydrochloride by two step chemical reactions, so it opens up a new way for the preparation of 3-Pyridineacetic Acid hydrochloride, and preparation process shortens greatly, easy and simple to handle, yield reaches more than 86%, and quality product obviously improves.
Embodiment
Embodiment 1
A) preparation process of 3-pyridine thioacetyl morphine quinoline
3-vinyl pyridine 86.8g is added 79g morphine quinoline, add sulphur 29g, heating reflux reaction 12 hours under the condition of stirring, reactant poured in the frozen water filter, crystal washs with frozen water, and seasoning promptly gets faint yellow crystallization 160.2g, yield 87.3% in the air.
B) preparation process of 3-Pyridineacetic Acid hydrochloride
3-pyridine thioacetyl morphine quinoline 160.2g and 182ml mixed in hydrochloric acid, reflux 6 hours is filtered, concentrating under reduced pressure, cooling crystallization, refining with concentrated hydrochloric acid 130ml, dry 107.6g white crystals 3-Pyridineacetic Acid hydrochloride, the yield 86% of getting.
Embodiment 2
A) preparation process of 3-pyridine thioacetyl morphine quinoline
3-vinyl pyridine 86.8g is added 79g morphine quinoline, add sulphur 29g under the condition of stirring, heating reflux reaction 14 hours is poured reactant in the frozen water into and to be filtered, and crystal washs with frozen water, and seasoning promptly gets faint yellow crystallization 165g, yield 90% in the air.
B) preparation process of 3-Pyridineacetic Acid hydrochloride
3-pyridine thioacetyl morphine quinoline 160.2g and 182ml mixed in hydrochloric acid, reflux 5 hours is filtered, concentrating under reduced pressure, cooling crystallization, refining with concentrated hydrochloric acid 110ml, dry 110g white crystals 3-Pyridineacetic Acid hydrochloride, the yield 88% of getting.
Claims (1)
1. the method for preparing the 3-Pyridineacetic Acid hydrochloride is characterized in that may further comprise the steps:
With the 3-vinyl pyridine is raw material, after finishing with morphine quinoline and sulfur reaction, pours in the frozen water and filters, and crystal washs with frozen water, and seasoning in air makes 3-pyridine thioacetyl morphine quinoline;
3-pyridine thioacetyl morphine quinoline is hydrolyzed with hydrochloric acid, after hydrolysis finishes, through activated carbon decolorizing, concentrating under reduced pressure, cooling crystallization makes the 3-Pyridineacetic Acid hydrochloride.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA200610069863XA CN101117331A (en) | 2006-08-05 | 2006-08-05 | Method for preparing 3-pyridine acetic acid hydrochloride |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA200610069863XA CN101117331A (en) | 2006-08-05 | 2006-08-05 | Method for preparing 3-pyridine acetic acid hydrochloride |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101117331A true CN101117331A (en) | 2008-02-06 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA200610069863XA Pending CN101117331A (en) | 2006-08-05 | 2006-08-05 | Method for preparing 3-pyridine acetic acid hydrochloride |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103242222A (en) * | 2013-05-22 | 2013-08-14 | 徐云根 | Preparation method of 3-pyridineacetic acid hydrochloride |
| CN106366034A (en) * | 2016-08-17 | 2017-02-01 | 南京红太阳生物化学有限责任公司 | Preparation method of 3-pyridylacetic acid hydrochloride |
| CN108467358A (en) * | 2018-05-29 | 2018-08-31 | 湖南华腾制药有限公司 | A kind of compound and preparation method thereof of 2- substitutions -5- pyridine acetic acid hydrochlorides |
| CN108530347A (en) * | 2018-05-29 | 2018-09-14 | 湖南华腾制药有限公司 | A kind of compound and preparation method thereof of 2- substitutions -4- pyridine acetic acid hydrochlorides |
-
2006
- 2006-08-05 CN CNA200610069863XA patent/CN101117331A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103242222A (en) * | 2013-05-22 | 2013-08-14 | 徐云根 | Preparation method of 3-pyridineacetic acid hydrochloride |
| CN103242222B (en) * | 2013-05-22 | 2016-04-27 | 徐云根 | A kind of preparation method of 3-Pyridineacetic Acid hydrochloride |
| CN106366034A (en) * | 2016-08-17 | 2017-02-01 | 南京红太阳生物化学有限责任公司 | Preparation method of 3-pyridylacetic acid hydrochloride |
| CN106366034B (en) * | 2016-08-17 | 2019-09-03 | 南京红太阳生物化学有限责任公司 | A kind of preparation method of 3-Pyridineacetic Acid hydrochloride |
| CN108467358A (en) * | 2018-05-29 | 2018-08-31 | 湖南华腾制药有限公司 | A kind of compound and preparation method thereof of 2- substitutions -5- pyridine acetic acid hydrochlorides |
| CN108530347A (en) * | 2018-05-29 | 2018-09-14 | 湖南华腾制药有限公司 | A kind of compound and preparation method thereof of 2- substitutions -4- pyridine acetic acid hydrochlorides |
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Open date: 20080206 |