CN101948397A - Method for preparing important intermediate of tapentadol hydrochloride analgesic - Google Patents
Method for preparing important intermediate of tapentadol hydrochloride analgesic Download PDFInfo
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- CN101948397A CN101948397A CN2010102732862A CN201010273286A CN101948397A CN 101948397 A CN101948397 A CN 101948397A CN 2010102732862 A CN2010102732862 A CN 2010102732862A CN 201010273286 A CN201010273286 A CN 201010273286A CN 101948397 A CN101948397 A CN 101948397A
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- 0 C*c1cc(Br)ccc1 Chemical compound C*c1cc(Br)ccc1 0.000 description 2
- OBFULUXHSSJMND-JBVHCYJISA-N C/C=C(/CNC)\C=C(/C)\N Chemical compound C/C=C(/CNC)\C=C(/C)\N OBFULUXHSSJMND-JBVHCYJISA-N 0.000 description 1
- QVWGKOYVOZJNRJ-ZETCQYMHSA-N CCC([C@@H](C)CN(C)C)=O Chemical compound CCC([C@@H](C)CN(C)C)=O QVWGKOYVOZJNRJ-ZETCQYMHSA-N 0.000 description 1
Abstract
The invention relates to a method for preparing an import intermediate of a tapentadol hydrochloride analgesic, which is (2S)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentyl-3-ol hydrochloride. The (2S)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentyl-3-ol hydrochloride with optical activity is obtained by the Grignard reaction of a compound II with optical activity and a compound III with optical activity. The Grignard reaction is performed by mixing magneson solution of the compound III and the tetrahydrofuran solution of the compound II at 5 to 10 DEG C and standing the mixed solution at room temperature overnight. The molar ratio of the compound II to the compound III is 0.8-1:1.0-1.5. The preparation method of the invention is not limited by a chiral column split instrument, solves the problem of processing enantiomers as waste chemicals, reduces production cost and is more suitable for large-batch industrial production.
Description
Technical field
The invention belongs to technical field of medicine synthesis, relate in being used for the treatment of, the severe acute pain he spray the preparation method of the important intermediate of his multiple medicines thing.The preparation method of (2S)-1-dimethylamino-3-(3-p-methoxy-phenyl)-2-methylpent-3-alcohol hydrochloride more specifically says so.
Background technology
He sprays he many (tapentadolhydrochloride) is by U.S. Johnson﹠amp; The oral pain alleviating medicine that acts on central nervous system of a kind of novelty of Johnson company research and development, it has two kinds of mechanism of action: a kind of is to act on opium μ 2 acceptors, by improving pain perception and emotional factor, the transmission of inhibition of pain in spinal cord, thereby the activity at the pallium position of influence and control perception pain; Another kind is the restraining effect to norepinephrine reuptake, suppress its heavy absorption and enter neurocyte, thereby the noradrenaline levels in the raising brain equally also plays analgesic activity.He sprays, and he is many not to rely on the metabolism activation effect, does not have the metabolism activation product, and various acute inflammations and neurodynia are all had potent effect, and its usefulness is between morphine and U-26225A.How he sprays him as a kind new medicine, in view of its good analgesic activities, is expected to be used for alleviating be grown up more than 18 years old acute and chronic to severe pain, especially can be used for alleviating the severe pain in the operation, and therefore, this product is easier to be accepted extensively and use by the patient.
He sprays, and he is many to have applied for patent protection in countries and regions such as Europe, the U.S., Germany, and relative patent mainly contains German Patent: DE102007019417; United States Patent (USP): US2008/0102130, US2009/0012180; European patent: EP1985292; World patent: WO2008/012046, WO2008/012047, WO2008/012283, WO2008/051617, WO2008/128739, WO2008/128740 etc., these patents are sprayed his many synthetic methods and therepic use etc. to him and are all protected.
He sprays his many chemical names: (-)-(1R, 2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl) phenolate hydrochlorate; He sprays his many chemical structural formulas and is disclosed as compound (+21) in EP-A 693475, (2R wherein, 3R)-it is to synthesize him to spray his many important intermediate that the hydrochloride of 1-dimethylamino-2-methyl 3-(3-p-methoxy-phenyl)-propane is disclosed as compound (+23), and its synthetic method is disclosed:
(2RS in compound (+23) synthetic, 3RS)-the synthetic of 1-dimethylamino-3-(3-p-methoxy-phenyl)-2-methylpent-3-alcohol hydrochloride is to carry out grignard reaction by 3-bromo phenyl methyl ether and 1-dimethylamino-2-methyl-propione, carry out the fractionation of diastereomer (i.e. two pairs of enantiomers) with trimethylchlorosilane/water hydrochloride precipitation in 2-butanone, carry out (2R by chiral column Chiral OD post, 3R) with (2S, 3S) fractionation of two of configuration kinds of enantiomer racemic mixtures.Obtain object (+23) through halogenation, elimination, reduction, fractionation again, this method is subjected to chiral column to split the instrument restriction and is not suitable for large batch of suitability for industrialized production.
In CN101228109A, then described a kind of with L-(-)-two-O, O '-to toluyl tartrate (L-DBTA) replace chiral column Chiral OD post carry out (2R, 3R) and (2S, 3S) fractionation of two of configuration kinds of enantiomer racemic mixtures.Though this method has realized large batch of preparation, still exist enantiomer to handle as waste chemicals, inadvisable economically at cost, be not suitable for large-scale industrialization production.In CN101495445A, described with (3-p-methoxy-phenyl) third-1-ketone be raw material preparation (2R, 3R)-method of 1-dimethylamino-2-methyl 3-(3-p-methoxy-phenyl)-propane (+23).In CN101495446A, described with 1-(3-(benzyloxy) phenyl) third-1-ketone be raw material preparation (2R, 3R)-method of 1-dimethylamino-2-methyl 3-(3-p-methoxy-phenyl)-propane (+23).
CN101495445A and CN101495446A all adopt be with L-DBTA earlier to N, N-dialkyl amido-2-alkyl-3-phenyl-1-acetone carries out R, the fractionation of two kinds of enantiomer racemic mixtures of S configuration.And then carry out reaction with grignard reagent.These class methods exist enantiomer to handle as waste chemicals, in the worthless economically shortcoming of cost.
Summary of the invention
The objective of the invention is to overcome the shortcoming of prior art with not enough, provide a kind of novel anodyne he spray his more important intermediates preparation, it is to adopt following step to carry out: optically active compound II and compound III are carried out grignard reaction, obtain optically active compound IV;
Wherein the mol ratio of Compound I I and compound III is 0.8-1; 1.0-1.5; Preferred mol ratio is 0.8: 1.
The present invention adopts 1-N; N-dimethyl-2-methyl-3-ketone is starting raw material; through L-(-)-two-O; O '-fractionation obtains (S)-1-N to toluyl tartrate (L-DBTA); N-dimethyl-2-methyl-3-ketone; then with 3-bromo phenylmethylether; carry out grignard reaction; carry out that the orientation of chirality is synthetic to obtain (S)-2-(S)-3-1-dimethylamino-3-(3-p-methoxy-phenyl)-2-methylpent-3-alcohol hydrochloride again through halogenation; reduction obtains (2R; 3R)-1-dimethylamino-2-methyl 3-(3-p-methoxy-phenyl)-propane (+23), at last through hydrolysis make he spray he many (+21).
Preparation method's of the present invention synthetic route is as follows:
The improved place of emphasis of the present invention is:
(1) optically active compound II and compound III are carried out grignard reaction, obtain optically active compound IV, having overcome needs the shortcoming that splits through chiral column after the reaction of DL thing, with (2S)-1-dimethylamino-3-(3-the p-methoxy-phenyl)-2-methylpent-3-alcohol hydrochloride intermediate of gained again through halogenation, reduction, hydrolysis make he spray he many (+21) through structural identification: products obtained therefrom is correct.
(2) preparation method of the present invention is not limited by chiral column fractionation instrument, and the problem that does not exist enantiomer to handle as waste chemicals has reduced production cost simultaneously, is more suitable for large batch of suitability for industrialized production.
Embodiment:
In order to explain enforcement of the present invention more fully, he sprays the preparation method of his more important intermediate (2S)-1-dimethylamino-3-(3-p-methoxy-phenyl)-2-methylpent-3-alcohol hydrochloride to the invention provides anodyne.These embodiments only are to explain rather than limit the scope of the invention.Wherein the preparation of optically active compound II is referring to reference example 1, and general formula (III) compound has commercially available; Solvent for use all has commercially available.
Reference example 1
The preparation of (+)-(S)-1-dimethylamino-2-methyl-propione
1-dimethylamino-2-methyl-propione 114.6 grams are added in the methyl alcohol, reflux is molten clear, add (-)-L-dibenzoyl tartaric acid 301.1 grams, adding distilled water again stirs molten clear, slowly stir (-)-L-dibenzoyl tartaric acid salt that cool to room temperature obtains 165.2 gram (S)-1-dimethylamino-2-methyl-propiones, mp157-158 ℃.([α]
D 20=-98.05, c=1%, methyl alcohol).
Free: as (+)-D-dibenzoyl tartaric acid salt of (S)-1-dimethylamino-2-methyl-propione to be added in entry and the dichloromethane solution, regulate PH to 8-9.Standing demix is used dichloromethane extraction.Organic phase merges, and after the drying, the pressure reducing and steaming solvent gets oily matter 42.2 grams.Under the nitrogen protection, underpressure distillation gets 33.2 gram product (+)-(S)-1-dimethylamino-2-methyl-propione [bp once more
1666 ℃] ([α]
D 22=+34.60; d
22 4=0.85517), yield 29%.
Preparation embodiment 1
(2S)-preparation of 1-dimethylamino-3-(3-p-methoxy-phenyl)-2-methylpent-3-alcohol hydrochloride
26.99 gram (1.11 moles) magnesium chips and 105 milliliters of anhydrous tetrahydro furans are joined in the dry anhydrous four-hole bottle, stir and drip the solution that is dissolved in 400 milliliters of 207.63g (1.11mol) 3-bromine phenylmethylethers in the anhydrous tetrahydro furan down, exothermic heat of reaction is slowly seethed with excitement reaction solution.Behind the solution that adds 3-bromine phenylmethylether, mixture heating up was refluxed 1 hour, be cooled to 5-10 ℃ then.Under this temperature, add be dissolved in the 400ml tetrahydrofuran (THF) 128.3 grams (0.89 mole) (S)-solution of 1-dimethylamino-2-methyl-propione.Reaction solution room temperature standing over night, and then be cooled to 5-10 ℃.Adding ammonium chloride solution decomposes form solution.Reaction mixture dilutes with ethyl acetate, isolates organic phase, the water ethyl acetate extraction.Organic phase dried over sodium sulfate after the merging.Remove solvent under reduced pressure, (212g) is dissolved in the 2-butanone with residue, and joins in the mixture of being made up of 120.6 gram trimethylchlorosilane-water.Go out 121.5 gram (2S)-1-dimethylamino-3-(3-p-methoxy-phenyl)-2-methylpent-3-alcohol hydrochlorides 4-5 ℃ of crystallization, fusing point is 198-199 ℃.Yield is 48%.
Preparation embodiment 2
(2S)-preparation of 1-dimethylamino-3-(3-p-methoxy-phenyl)-2-methylpent-3-alcohol hydrochloride
26.99 gram (1.11 moles) magnesium chips and 105 milliliters of anhydrous tetrahydro furans are joined in the dry anhydrous four-hole bottle, stir and drip the solution that is dissolved in the gram of 280.6 in 400 milliliters of anhydrous tetrahydro furans (1.5mol) 3-bromine phenylmethylether down, exothermic heat of reaction is slowly seethed with excitement reaction solution.Behind the solution that adds 3-bromine phenylmethylether, mixture heating up was refluxed 1 hour, be cooled to 5-10 ℃ then.Under this temperature, add be dissolved in the 400ml tetrahydrofuran (THF) 114.6 grams (0.8 mole) (S)-solution of 1-dimethylamino-2-methyl-propione.Reaction solution room temperature standing over night, and then be cooled to 5-10 ℃.Adding ammonium chloride solution decomposes form solution.Reaction mixture dilutes with ethyl acetate, isolates organic phase, the water ethyl acetate extraction.Organic phase dried over sodium sulfate after the merging.Remove solvent under reduced pressure, (212g) is dissolved in the 2-butanone with residue, and joins in the mixture of being made up of 120.6 gram trimethylchlorosilane-water.Go out 114.0 gram (2S)-1-dimethylamino-3-(3-p-methoxy-phenyl)-2-methylpent-3-alcohol hydrochlorides 4-5 ℃ of crystallization, fusing point is 198-199 ℃.Yield is 50%.
(2S)-1-dimethylamino-3-(3-the p-methoxy-phenyl)-2-methylpent-3-alcohol hydrochloride of the present invention's preparation is directly used in (2R, 3R)-preparation (+23) of 1-dimethylamino-2-methyl 3-(3-p-methoxy-phenyl)-propane, then through 1 one-step hydrolysis reaction made final he spray he many (+21), through structural identification: products obtained therefrom is correct, and the preparation method of its reference is as follows.
Application Example 1:
(2S)-preparation of [3-chloro-3-(3-p-methoxy-phenyl)-2-methyl amyl]-dimethylamine hydrochloride
At room temperature, join in 10 milliliters of sulfur oxychlorides (2S)-1-dimethylamino-3-(3-p-methoxy-phenyl)-2-methylpent-3-alcohol hydrochloride 10.0 grams.Feed drying nitrogen 2 hours subsequently to remove excessive sulfur oxychloride.Again add sulfur oxychloride relief reaction mixture sat 12 hours, and then feed drying nitrogen, remove excessive sulfur oxychloride.Residue is dissolved in the 2-butanone, separates out crystallization and be (2S)-[3-chloro-3-(3-p-methoxy-phenyl)-2-methyl amyl]-dimethylamine hydrochloride 9.6 grams, yield 91%.
Application Example 2
(+)-(2R, 3R)-preparation of [3-(3-p-methoxy-phenyl)-2-methyl amyl]-dimethylamine hydrochloride
Restrain sodium borohydrides with 31 and add in the reaction flasks, dropping 46 gram exsiccant zinc chloride were dissolved in the solution in the anhydrous ethyl acetate under the adding ethyl acetate stirred.Stir after 12 hours that decant goes out from resulting zinc borohydride suspension, and be added drop-wise in 200 milliliters of anhydrous ethyl acetates that contain 9.8 gram (2S)-[3-chloro-3-(3-p-methoxy-phenyl)-2-methyl amyl]-dimethylamine hydrochlorides.At room temperature reaction mixture was stirred 72 hours, under the ice bath cooling, be added drop-wise in the saturated ammonium chloride solution then.After being separated, ether is used the saturated common salt water washing mutually; With under vacuum, steaming solvent after the dried over sodium sulfate.Obtain 7.3 gram (2R)-[3-(3-p-methoxy-phenyl)-2-methyl amyl]-dimethylamine-borane title complexs, again it is dissolved in the anhydrous methanol.After adding triphenyl phosphine mixture heating up was refluxed 18 hours.Remove the back residue that desolvates by distillation and join in the hydrochloric acid, wash with ethyl acetate then.Regulating water layer with soda-lye is PH8, uses dichloromethane extraction, merges organic phase, behind the anhydrous magnesium sulfate drying, removes solvent under reduced pressure, gets the 5.2g residue.This residue is dissolved in the 2-butanone, behind adding 12 gram trimethylchlorosilane/2 ml waters, separates out crystallization 4.3g.Mp:163-164 ℃; [α]
D RT=+25.20 (c=0.95, methyl alcohol).Yield is 50%.
Application Example 3
(-)-(1R, 2R)-preparation of 3-(3-dimethylamino-1-ethyl-2-methyl-propyl) phenolate hydrochlorate (he spray him many)
(+)-(2R with 4.3 grams, 3R)-[3-(3-p-methoxy-phenyl)-2-methyl amyl]-dimethylamine hydrochloride joins in the reaction flask, add concentrated hydrochloric acid, be heated to back flow reaction then 2 hours, reaction is finished, cooling, concentrating under reduced pressure, the simplification of resistates sodium bicarbonate is handled to pH value 8, uses dichloromethane extraction, the combined dichloromethane layer, add anhydrous sodium sulfate drying, evaporated under reduced pressure methylene dichloride then, resistates 4 grams, add the 2-butanone dissolving, and join in the mixture of forming by 24.0 gram trimethylchlorosilane-water.The crystallization that filtration obtains, 3.8 grams (-)-(1R, 2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl) phenolate hydrochlorate.Fusing point: 194～196 ℃; [α]
D RT=+24.5 (c=1.10, methyl alcohol).
Ultimate analysis: analytical value: C 65.10; H 9.393; N 5.44; Cl 13.74; O 6.27
Theoretical value: C 65.23; H 9.38; N 5.49; Cl 13.75; O 6.21.
Claims (2)
- An anodyne he spray the preparation method of his many intermediates (2S)-1-dimethylamino-3-(3-p-methoxy-phenyl)-2-methylpent-3-alcohol hydrochloride (IV), it is characterized in that optically active compound II and compound III are carried out grignard reaction, obtain optically active compound IV;
Wherein the mol ratio of Compound I I and compound III is 0.8-1: 1.0-1.5. - 2. the described preparation method of claim 1, wherein said grignard reaction is under 5-10 ℃ the azoviolet solution of compound III to be mixed with the tetrahydrofuran solution of Compound I I, then the room temperature standing over night.
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| CN2010102732862A CN101948397A (en) | 2010-09-07 | 2010-09-07 | Method for preparing important intermediate of tapentadol hydrochloride analgesic |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012023147A1 (en) * | 2010-08-16 | 2012-02-23 | Indoco Remedies Limited | Process for the preparation of tapentadol |
| CN102557851A (en) * | 2011-12-13 | 2012-07-11 | 安徽省新星药物开发有限责任公司 | New method for synthesizing tapentadol hydrochloride and analogue of tapentadol hydrochloride |
| CN102617501A (en) * | 2011-01-31 | 2012-08-01 | 中国科学院上海药物研究所 | Substituted valeramide compound, preparation method and application thereof |
| CN102711461A (en) * | 2009-12-29 | 2012-10-03 | Mapi医药公司 | Intermediate compounds and processes for the preparation of tapentadol and related compounds |
| CN102838493A (en) * | 2012-09-20 | 2012-12-26 | 合肥市新星医药化工有限公司 | Synthesis method for 3-[(1R, 2R)-3-( dimethylamino)-1-ethyl-2-methylpropyl] phenol |
| EP2545028A4 (en) * | 2011-01-27 | 2013-07-03 | Symed Labs Ltd | A novel stereospecific synthesis of (-) (2s,3s)-1-dimethylamino-3-(3-methoxyphenyl)-2-methyl pentan-3-ol |
| CN103655531A (en) * | 2013-12-24 | 2014-03-26 | 南京艾德凯腾生物医药有限责任公司 | Tapentadol (hydrochloride) oral solution and preparation method thereof |
| KR20190017056A (en) * | 2011-03-04 | 2019-02-19 | 그뤼넨탈 게엠베하 | Aqueous pharmaceutical formulation of tapentadol for oral administration |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1163884A (en) * | 1996-03-13 | 1997-11-05 | 格吕伦塔尔有限公司 | Dimethyl-(3-aryl-but-3-enyl)-amine compounds as pharmaceutical active ingredients |
| US20020010178A1 (en) * | 1994-07-23 | 2002-01-24 | Gruenenthal Gmbh | 1-phenyl-3-dimethylaminopropane compounds with a pharmacological effect |
| EP1985292A1 (en) * | 2007-04-23 | 2008-10-29 | Grünenthal GmbH | Titration of tapentadol |
| CN101495445A (en) * | 2006-07-24 | 2009-07-29 | 格吕伦塔尔有限公司 | Process for the preparation of (1R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol |
-
2010
- 2010-09-07 CN CN2010102732862A patent/CN101948397A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020010178A1 (en) * | 1994-07-23 | 2002-01-24 | Gruenenthal Gmbh | 1-phenyl-3-dimethylaminopropane compounds with a pharmacological effect |
| CN1163884A (en) * | 1996-03-13 | 1997-11-05 | 格吕伦塔尔有限公司 | Dimethyl-(3-aryl-but-3-enyl)-amine compounds as pharmaceutical active ingredients |
| CN101495445A (en) * | 2006-07-24 | 2009-07-29 | 格吕伦塔尔有限公司 | Process for the preparation of (1R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol |
| EP1985292A1 (en) * | 2007-04-23 | 2008-10-29 | Grünenthal GmbH | Titration of tapentadol |
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102711461A (en) * | 2009-12-29 | 2012-10-03 | Mapi医药公司 | Intermediate compounds and processes for the preparation of tapentadol and related compounds |
| WO2012023147A1 (en) * | 2010-08-16 | 2012-02-23 | Indoco Remedies Limited | Process for the preparation of tapentadol |
| US8853456B2 (en) | 2010-08-16 | 2014-10-07 | Indoco Remedies Limited | Process for the preparation of tapentadol |
| EP2545028A4 (en) * | 2011-01-27 | 2013-07-03 | Symed Labs Ltd | A novel stereospecific synthesis of (-) (2s,3s)-1-dimethylamino-3-(3-methoxyphenyl)-2-methyl pentan-3-ol |
| CN102617501A (en) * | 2011-01-31 | 2012-08-01 | 中国科学院上海药物研究所 | Substituted valeramide compound, preparation method and application thereof |
| KR20190017056A (en) * | 2011-03-04 | 2019-02-19 | 그뤼넨탈 게엠베하 | Aqueous pharmaceutical formulation of tapentadol for oral administration |
| KR102051800B1 (en) | 2011-03-04 | 2019-12-04 | 그뤼넨탈 게엠베하 | Aqueous pharmaceutical formulation of tapentadol for oral administration |
| CN102557851A (en) * | 2011-12-13 | 2012-07-11 | 安徽省新星药物开发有限责任公司 | New method for synthesizing tapentadol hydrochloride and analogue of tapentadol hydrochloride |
| CN102557851B (en) * | 2011-12-13 | 2014-03-26 | 安徽省新星药物开发有限责任公司 | New method for synthesizing tapentadol hydrochloride and analogue of tapentadol hydrochloride |
| CN102838493A (en) * | 2012-09-20 | 2012-12-26 | 合肥市新星医药化工有限公司 | Synthesis method for 3-[(1R, 2R)-3-( dimethylamino)-1-ethyl-2-methylpropyl] phenol |
| CN102838493B (en) * | 2012-09-20 | 2014-09-03 | 合肥市新星医药化工有限公司 | Synthesis method for 3-[(1R, 2R)-3-( dimethylamino)-1-ethyl-2-methylpropyl] phenol |
| CN103655531A (en) * | 2013-12-24 | 2014-03-26 | 南京艾德凯腾生物医药有限责任公司 | Tapentadol (hydrochloride) oral solution and preparation method thereof |
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