CN104402764A - Preparation method for entacapone - Google Patents

Preparation method for entacapone Download PDF

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Publication number
CN104402764A
CN104402764A CN201410689683.6A CN201410689683A CN104402764A CN 104402764 A CN104402764 A CN 104402764A CN 201410689683 A CN201410689683 A CN 201410689683A CN 104402764 A CN104402764 A CN 104402764A
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CN
China
Prior art keywords
entacapone
virahol
washing
cooled
reaction vessel
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
Application number
CN201410689683.6A
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Chinese (zh)
Inventor
杨会来
毛杰
孙学喜
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Wan Hui Pharmaceutical (anhui) Co Ltd
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Wan Hui Pharmaceutical (anhui) Co Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Wan Hui Pharmaceutical (anhui) Co Ltd filed Critical Wan Hui Pharmaceutical (anhui) Co Ltd
Priority to CN201410689683.6A priority Critical patent/CN104402764A/en
Publication of CN104402764A publication Critical patent/CN104402764A/en
Pending legal-status Critical Current

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Abstract

The invention discloses a preparation method for entacapone. The preparation method comprises the following steps: 3, 4-dyhydroxyl-5-nitrobenzaldehyde, N, N-diethyl cyanoacetamide, piperidine and acetic acid are added into isopropanol to be subjected to heating backflow reaction, and finally the reactants are subjected to recrystallization in the isopropanol, so that the entacapone is prepared. The prepared entacapone has excellent quality and high purity, and the preparation method is simple, low in energy consumption and low in cost.

Description

A kind of preparation method of Entacapone
 
Technical field
The present invention relates to a kind of preparation method of pharmaceutical raw material, specifically a kind of preparation method of Entacapone.
Background technology
Entacapone (entacapone) is a specific peripheral catecholamine-O-methyltransferase inhibitors (COMTI, catechol-O-methyltransferase), is a kind new medicine of Orion development and production, and trade(brand)name comtan(jade-like stone is red).Within 1998, in listings such as Britain, Germany, Denmark, more than 70 the countries and regions listing in the whole world so far, E is used for the assisting therapy of Parkinson's disease (PD), is the adjuvant drug of levodopa.
Summary of the invention
The technical problem to be solved in the present invention is to provide a kind of preparation method of Entacapone, and its cost is low, and yield is high, and Z isomer content is low.
Technical scheme of the present invention is:
A preparation method for Entacapone, comprises the steps:
(1), first Virahol is joined in reaction vessel, and then by 3,4-dihydroxyl-5-nitrobenzaldehyde, N, N-diethylcyanoacetamide, piperidines, acetic acid join reflux 2.5-3.5h in reaction vessel, after reaction terminates, reaction solution are cooled to room temperature, and gained throw out is at room temperature stirred spend the night, finally be cooled to 0-5 DEG C, after filtration, washing, vacuum-drying, obtain Entacapone piperidinium salt;
(2), the Entacapone piperidinium salt that step (1) obtains is joined in Virahol under 20-30 DEG C of condition, is cooled to 0-5 DEG C, then filters, washs, vacuum-drying, obtain product.
The mass ratio of 3,4-dihydroxyl-5-nitrobenzaldehydes, N, N-diethylcyanoacetamide, piperidines, acetic acid and Virahol in described step (1) reaction vessel is 1: 1.50-1.55: 0.65-0.75: 0.45-0.55: 7.5-8.5.
Washing in described step (1) adopts washed with isopropyl alcohol.
The concrete steps of washing adopt volume ratio to be Virahol and the water washing of 1:2 in described step (2), finally washes with water.
Advantage of the present invention:
Entacapone quality prepared by the present invention is good, and purity is high, and preparation method is simple, and less energy consumption, cost is low.
Embodiment
A preparation method for Entacapone, comprises the steps:
(1), first 700ml Virahol is joined in reaction vessel, and then by 70g 3,4-dihydroxyl-5-nitrobenzaldehyde, 107gN, N-diethylcyanoacetamide, 48.8g piperidines, 34.4g acetic acid join reflux 2.5-3.5h in reaction vessel, after reaction terminates, reaction solution are cooled to room temperature, and gained throw out is at room temperature stirred spend the night, finally be cooled to 0-5 DEG C, after filtration, 140ml washed with isopropyl alcohol, vacuum-drying, obtain Entacapone piperidinium salt;
(2), the Entacapone piperidinium salt that step (1) obtains is joined in 600ml Virahol under 20-30 DEG C of condition, be cooled to 0-5 DEG C, Virahol and the water washing of then filtering, adopting 240ml volume ratio to be 1:2, finally wash with water, vacuum-drying, obtains product.

Claims (4)

1. a preparation method for Entacapone, is characterized in that, comprises the steps:
(1), first Virahol is joined in reaction vessel, and then by 3,4-dihydroxyl-5-nitrobenzaldehyde, N, N-diethylcyanoacetamide, piperidines, acetic acid join reflux 2.5-3.5h in reaction vessel, after reaction terminates, reaction solution are cooled to room temperature, and gained throw out is at room temperature stirred spend the night, finally be cooled to 0-5 DEG C, after filtration, washing, vacuum-drying, obtain Entacapone piperidinium salt;
(2), the Entacapone piperidinium salt that step (1) obtains is joined in Virahol under 20-30 DEG C of condition, is cooled to 0-5 DEG C, then filters, washs, vacuum-drying, obtain product.
2. the preparation method of a kind of Entacapone according to claim 1, it is characterized in that: in described step (1) reaction vessel 3, the mass ratio of 4-dihydroxyl-5-nitrobenzaldehyde, N, N-diethylcyanoacetamide, piperidines, acetic acid and Virahol is 1: 1.50-1.55: 0.65-0.75: 0.45-0.55: 7.5-8.5.
3. the preparation method of a kind of Entacapone according to claim 1, is characterized in that: the washing in described step (1) adopts washed with isopropyl alcohol.
4. the preparation method of a kind of Entacapone according to claim 1, is characterized in that: the concrete steps of washing adopt volume ratio to be Virahol and the water washing of 1:2 in described step (2), finally washes with water.
CN201410689683.6A 2014-11-26 2014-11-26 Preparation method for entacapone Pending CN104402764A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201410689683.6A CN104402764A (en) 2014-11-26 2014-11-26 Preparation method for entacapone

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201410689683.6A CN104402764A (en) 2014-11-26 2014-11-26 Preparation method for entacapone

Publications (1)

Publication Number Publication Date
CN104402764A true CN104402764A (en) 2015-03-11

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CN201410689683.6A Pending CN104402764A (en) 2014-11-26 2014-11-26 Preparation method for entacapone

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105061259A (en) * 2015-08-25 2015-11-18 重庆植恩药业有限公司 Preparing method for entacapone A-type crystals
CN105237437A (en) * 2015-12-03 2016-01-13 重庆植恩药业有限公司 Entacapone impurity compound and preparation method thereof

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0426468A2 (en) * 1989-11-03 1991-05-08 Orion-Yhtymä Oy Stabile polymorphic form of (E)-N,N-diethyl-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl) acrylamide and the process for its preparation
CN1926095A (en) * 2003-12-29 2007-03-07 苏文生命科学有限公司 Improved method for preparing entacapone
WO2007054950A1 (en) * 2005-11-09 2007-05-18 Usv Limited A process for the preparation of highly pure (e) n,n-diethyl-2-cyano-3-(3,4-dihydroxy- 5-nitro phenyl) acrylamide (entacapone)
CN101379024A (en) * 2006-02-06 2009-03-04 奥赖恩公司 Process for manufacturing entacapone
US20090326062A1 (en) * 2007-02-13 2009-12-31 Chemo Iberica, SA Process for preparing entacapone substantially free of z-isomer, synthesis intermediates thereof and a new crystalline form
CN102120726A (en) * 2010-01-08 2011-07-13 浙江华海药业股份有限公司 New preparation method of (2E)-2-cyano-3-(3,4-dihydroxy-5-nitrobenzene)-N,N-diethyl-2-acrylamide
CN103130681A (en) * 2013-03-19 2013-06-05 上海奥博生物医药技术有限公司 Novel method for preparing entacapone

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0426468A2 (en) * 1989-11-03 1991-05-08 Orion-Yhtymä Oy Stabile polymorphic form of (E)-N,N-diethyl-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl) acrylamide and the process for its preparation
CN1926095A (en) * 2003-12-29 2007-03-07 苏文生命科学有限公司 Improved method for preparing entacapone
WO2007054950A1 (en) * 2005-11-09 2007-05-18 Usv Limited A process for the preparation of highly pure (e) n,n-diethyl-2-cyano-3-(3,4-dihydroxy- 5-nitro phenyl) acrylamide (entacapone)
CN101379024A (en) * 2006-02-06 2009-03-04 奥赖恩公司 Process for manufacturing entacapone
US20090326062A1 (en) * 2007-02-13 2009-12-31 Chemo Iberica, SA Process for preparing entacapone substantially free of z-isomer, synthesis intermediates thereof and a new crystalline form
CN102120726A (en) * 2010-01-08 2011-07-13 浙江华海药业股份有限公司 New preparation method of (2E)-2-cyano-3-(3,4-dihydroxy-5-nitrobenzene)-N,N-diethyl-2-acrylamide
CN103130681A (en) * 2013-03-19 2013-06-05 上海奥博生物医药技术有限公司 Novel method for preparing entacapone

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105061259A (en) * 2015-08-25 2015-11-18 重庆植恩药业有限公司 Preparing method for entacapone A-type crystals
CN105237437A (en) * 2015-12-03 2016-01-13 重庆植恩药业有限公司 Entacapone impurity compound and preparation method thereof

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Application publication date: 20150311