AU2016102240A4 - Benzene carboxamide pharmaceutical intermediates trans-4-N- benzyloxycarbonyl-aminomethyl-cyclohexane-1-carboxylic acid synthesis method - Google Patents
Benzene carboxamide pharmaceutical intermediates trans-4-N- benzyloxycarbonyl-aminomethyl-cyclohexane-1-carboxylic acid synthesis method Download PDFInfo
- Publication number
- AU2016102240A4 AU2016102240A4 AU2016102240A AU2016102240A AU2016102240A4 AU 2016102240 A4 AU2016102240 A4 AU 2016102240A4 AU 2016102240 A AU2016102240 A AU 2016102240A AU 2016102240 A AU2016102240 A AU 2016102240A AU 2016102240 A4 AU2016102240 A4 AU 2016102240A4
- Authority
- AU
- Australia
- Prior art keywords
- solution
- aminomethyl
- cyclohexane
- benzyloxycarbonyl
- carboxylic acid
- 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.)
- Ceased
Links
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Benzene carboxamide pharmaceutical intermediates trans -4-N benzyloxycarbonyl-aminomethyl-cyclohexane- 1 -carboxylic acid synthesis method , comprising the following steps: equipped with a stirrer, the reaction vessel was added 0.043 mol trans-4-aminomethyl cyclohexane-1-carboxylic acid (2), 30-40ml sodium sulfite solution, the temperature of the solution is reduced to 2 -5 0C, controlling the agitation speed 130-160rpm, dropwise added 0.05-0.053mol benzyloxycarbonyl amide (3), control dropwise addition time in 90-120min, whereupon white crystals precipitated, the resulting crystals were dissolved in 300ml potassium chloride solution, added oxalic acid solution to adjust solution pH to 6-7, the temperature of the solution is reduced to 1--3 0C, white precipitate, suction filtered, washed with saline solution, dehydrated with dehydrating agent, recrystallization in solution of triethylamine, got white needle crystals trans -4-N benzyloxycarbonyl-aminomethyl-cyclohexane-1-carboxylic acid.
Description
Benzene carboxamide pharmaceutical intermediates trans-4-N-benzyloxycarbonyl-aminomethyl-cyclohexane-l-carboxylic acid synthesis method
TECHNICAL FIELD
The present invention relates to benzene carboxamide pharmaceutical intermediates trans-4-N- benzyloxycarbonyl-aminomethyl-cyclohexane-1 -carboxylic acid synthesis method.
BACKGROUND ART
Benzene carboxamide plays a major role in the a receptor, directly excited a receptor, compared with norepinephrine weaker but have more lasting effect on cardiovascular similar to norepinephrine. It can shrink blood vessels, has sustained systolic blood pressure and diastolic blood pressure, but also it can enhance myocardial contractility, heart normal output changed little, can make the patient's shock increase in cardiac output. The excitement of the heart rate is not very significant; rarely cause arrhythmia, no central nervous system stimulant. trans-4-N-benzyloxycarbonyl-aminomethyl-cyclohexane-1-carboxylic acid as benzene carboxamide drug intermediates, its synthesis method is of great economic significance for improving drug synthesis product quality, reducing the by-product content.
SUMMARY OF THE INVENTION
Object of the present invention is to provide benzene carboxamide pharmaceutical intermediates trans -4-N- benzyloxycarbonyl-aminomethyl-cyclohexane-1 -carboxylic acid synthesis method , comprising the following steps: (i)equipped with a stirrer, the reaction vessel was added 0.043 mol trans-4-aminomethyl cyclohexane-1-carboxylic acid (2), 30-40ml sodium sulfite solution, the temperature of the solution is reduced to 2 -5 °C, controlling the agitation speed 130-160rpm, drop wise added 0.05-0.053mol benzyloxycarbonyl amide (3), control dropwise addition time in 90-120min, whereupon white crystals precipitated, the resulting crystals were dissolved in 300ml potassium chloride solution, added oxalic acid solution to adjust solution pH to 6-7, the temperature of the solution is reduced to 1—3°C, white precipitate, suction filtered, washed with saline solution, dehydrated with dehydrating agent, recrystallization in solution of triethylamine, got white needle crystals trans -4-N-benzyloxycarbonyl-aminomethyl-cyclohexane-1-carboxylic acid (1); wherein sodium sulfite solution in step (i) has a mass fraction of 30-35%, potassium chloride solution in step (i) has a mass fraction of 10-15%, oxalic acid solution in step (i) has a mass fraction of 20-30%, saline solution in step (i) is any one of potassium nitrate solution or sodium sulfate solution; dehydrating agent in step (i) is any one of anhydrous potassium carbonate or anhydrous calcium sulfate; triethylamine in step (i) has a mass fraction of 90-95%.
The throughout reaction process can be summarized using the following reaction formula:
Advantage of the present invention is that: the reaction intermediate links are reduced, reducing the reaction temperature and reaction time, improving the reaction yield. DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS OF THE INVENTION Embodiment 1
Equipped with a stirrer, the reaction vessel was added 0.043 mol trans-4-aminomethyl cyclohexane-1-carboxylic acid (2), 30 ml sodium sulfite solution with a mass fraction of 30%, the temperature of the solution is reduced to 2 °C, controlling the agitation speed 130 rpm, dropwise added 0.05 mol benzyloxycarbonyl amide (3), control dropwise addition time in 90 min, whereupon white crystals precipitated, the resulting crystals were dissolved in 300ml potassium chloride solution with a mass fraction of 10%, added oxalic acid solution to adjust solution pH to 6, the temperature of the solution is reduced to 1 °C, white precipitate, suction filtered, washed with potassium nitrate solution, dehydrated with anhydrous potassium carbonate dehydrating agent, recrystallization in solution of triethylamine with a mass fraction of 90%, got white needle crystals trans-4-N- benzyloxycarbonyl-aminomethyl-cyclohexane-1-carboxylic acid 10.64 g, yield 85%.
Embodiment 2
Equipped with a stirrer, the reaction vessel was added 0.043 mol trans-4-aminomethyl cyclohexane-1-carboxylic acid (2), 30 ml sodium sulfite solution with a mass fraction of 32%, the temperature of the solution is reduced to 3 °C, controlling the agitation speed 140 rpm, dropwise added 0.051 mol benzyloxycarbonyl amide (3), control dropwise addition time in 110 min, whereupon white crystals precipitated, the resulting crystals were dissolved in 300ml potassium chloride solution with a mass fraction of 12%, added oxalic acid solution to adjust solution pH to 6, the temperature of the solution is reduced to 2 °C, white precipitate, suction filtered, washed with sodium sulfate solution, dehydrated with anhydrous calcium sulfate dehydrating agent, recrystallization in solution of triethylamine with a mass fraction of 92%, got white needle crystals trans-4-N- benzyloxycarbonyl-aminomethyl-cyclohexane-1-carboxylic acid 11.01 g, yield 88%.
Embodiment 3
Equipped with a stirrer, the reaction vessel was added 0.043 mol trans-4-aminomethyl cyclohexane-1-carboxylic acid (2), 30 ml sodium sulfite solution with a mass fraction of 35%, the temperature of the solution is reduced to 5 °C, controlling the agitation speed 160 rpm, drop wise added 0.053 mol benzyloxycarbonyl amide (3), control drop wise addition time in 120 min, whereupon white crystals precipitated, the resulting crystals were dissolved in 300ml potassium chloride solution with a mass fraction of 15%, added oxalic acid solution to adjust solution pH to 7, the temperature of the solution is reduced to 3 °C, white precipitate, suction filtered, washed with potassium nitrate solution, dehydrated with anhydrous potassium carbonate dehydrating agent, recrystallization in solution of triethylamine with a mass fraction of 95%, got white needle crystals trans-4-N- benzyloxycarbonyl-aminomethyl-cyclohexane-1-carboxylic acid 11.39 g, yield 91%.
While a number of preferred embodiments have been described, it will be appreciated by persons skilled in the art that numerous variations and/or modifications may be made to the invention without departing from the spirit or scope of the invention as broadly described. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive.
Claims (4)
1. Benzene carboxamide pharmaceutical intermediates trans -4-N-benzyloxycarbonyl-aminomethyl-cyclohexane-l -carboxylic acid synthesis method , comprising the following steps: (i) equipped with a stirrer, the reaction vessel was added 0.043 mol trans-4-aminomethyl cyclohexane-1-carboxylic acid (2), 30-40ml sodium sulfite solution, the temperature of the solution is reduced to 2 -5 °C, controlling the agitation speed 130-160rpm, drop wise added 0.05-0.053mol benzyloxycarbonyl amide (3), control dropwise addition time in 90-120min, whereupon white crystals precipitated, the resulting crystals were dissolved in 300ml potassium chloride solution, added oxalic acid solution to adjust solution pH to 6-7, the temperature of the solution is reduced to 1—3°C, white precipitate, suction filtered, washed with saline solution, dehydrated with dehydrating agent, recrystallization in solution of triethylamine, got white needle crystals trans -4-N-benzyloxycarbonyl-aminomethyl-cyclohexane-1-carboxylic acid (1); wherein sodium sulfite solution in step (i) has a mass fraction of 30-35%, potassium chloride solution in step (i) has a mass fraction of 10-15%, oxalic acid solution in step (i) has a mass fraction of 20-30%.
2. Benzene carboxamide pharmaceutical intermediates trans -4-N- benzyloxycarbonyl-aminomethyl-cyclohexane-1 -carboxylic acid synthesis method according to claim 1 wherein saline solution in step (i) is any one of potassium nitrate solution or sodium sulfate solution.
3. Benzene carboxamide pharmaceutical intermediates trans -4-N- benzyloxycarbonyl-aminomethyl-cyclohexane-1 -carboxylic acid synthesis method according to claim 1 wherein dehydrating agent in step (i) is any one of anhydrous potassium carbonate or anhydrous calcium sulfate.
4. Benzene carboxamide pharmaceutical intermediates trans -4-N- benzyloxycarbonyl-aminomethyl-cyclohexane-1 -carboxylic acid synthesis method according to claim 1 wherein triethylamine in step (i) has a mass fraction of 90-95%.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510981710.1A CN105566165A (en) | 2015-12-24 | 2015-12-24 | Cyclobenzo carboxamide drug intermediate trans-4-N-benzyloxycarbonylaminomethyl cyclohexane-1-carboxylic acid synthetic method |
| CN2015109817101 | 2015-12-24 | ||
| CN201610813929.5A CN106397244A (en) | 2015-12-24 | 2016-09-11 | Synthesis method of cyclobenzo carboxamide medicine intermediate trans-4-N-benzyloxycarbonylaminomethyl cyclohexane-1-carboxylic acid |
| CN2016108139295 | 2016-09-11 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2016102240A4 true AU2016102240A4 (en) | 2017-02-16 |
Family
ID=57996401
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2016102240A Ceased AU2016102240A4 (en) | 2015-12-24 | 2016-12-23 | Benzene carboxamide pharmaceutical intermediates trans-4-N- benzyloxycarbonyl-aminomethyl-cyclohexane-1-carboxylic acid synthesis method |
Country Status (1)
| Country | Link |
|---|---|
| AU (1) | AU2016102240A4 (en) |
-
2016
- 2016-12-23 AU AU2016102240A patent/AU2016102240A4/en not_active Ceased
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105085322B (en) | The Preparation Method And Their Intermediate of the intermediates of AHU 377 and the preparation method of intermediate | |
| CN101012217A (en) | Method of synthesizing landiolol hydrochloride | |
| AU2016102240A4 (en) | Benzene carboxamide pharmaceutical intermediates trans-4-N- benzyloxycarbonyl-aminomethyl-cyclohexane-1-carboxylic acid synthesis method | |
| CN104557692B (en) | A kind of preparation method of pantoprazole intermediate 2- chloromethyls -3,4- dimethoxy pyridine hydrochlorides | |
| CN106749187A (en) | A kind of synthetic method of phthalyl Amlodipine | |
| CN110642753A (en) | Amino acid derivative | |
| SU1093246A3 (en) | Process for preparing 3,4-bis-substituted 1,2,5-oxa-diazol-2-oxides or their pharmaceutically acceptable acid addition salts | |
| CN108299226A (en) | A kind of synthetic method of AHU377 calcium salts | |
| CN106699604A (en) | Sacubitril and preparation method of midbody of sacubitril | |
| AU2016102318A4 (en) | Perhexiline drug intermediates α-(2,2- diphenyl-vinyl) pyridine synthesis method | |
| EP2533644B1 (en) | Diazeniumdiolate cyclopentyl derivatives | |
| CN106397244A (en) | Synthesis method of cyclobenzo carboxamide medicine intermediate trans-4-N-benzyloxycarbonylaminomethyl cyclohexane-1-carboxylic acid | |
| CN101844991B (en) | Preparation method of L-leucine nitrate | |
| AU2016102180A4 (en) | Farrerol drug intermediates 2,6-dimethyl-acetanilide synthesis method | |
| AU2016102279A4 (en) | Alinidine drug intermediate 2- (N- allyl--N-2,6- dichlorophenyl) amino imidazoline synthesis method | |
| AU2016102299A4 (en) | Atropine drug intermediates acetonedicarboxylic acid synthesis method | |
| AU2016102185A4 (en) | Celiprolol pharmaceutical intermediate 3- (4-ethoxyphenyl) -1, 1-diethyl-urea synthesis method | |
| CN106431952A (en) | Synthetic method of capobenic acid intermediate epsilon-(3, 4, 5-trimethoxybenzoylamino]acetic acid | |
| AU2016102190A4 (en) | Method for synthesizing ticlopidine hydrochloride pharmaceutical intermediates 2-nitro-vinyl thiophene | |
| AU2018100398A4 (en) | Blood circulation diagnosis medication o-sulfonamide benzoic acid synthesis method | |
| AU2016102276A4 (en) | Tranilast drug intermediates 3,4-dimethoxybenzaldehyde synthesis method | |
| CN109438397B (en) | Synthetic method of sofosbuvir intermediate | |
| AU2016102241A4 (en) | Calcipotriene acid drug intermediates ε- (3,4,5- trimethoxybenzoyl amino) - acetic acid synthesis method | |
| AU2016102310A4 (en) | Biphenyldicarboxylate drug intermediates 3 - methoxy - 4, 5 - methyl 2 oxo benzoic acid methyl ester synthesis method | |
| CN103755727B (en) | Preparation method of brinzolamide intermediate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FGI | Letters patent sealed or granted (innovation patent) | ||
| MK22 | Patent ceased section 143a(d), or expired - non payment of renewal fee or expiry |