CN101235011A - N-amino-1,2-cyclopentanediformylimine and preparation method thereof - Google Patents
N-amino-1,2-cyclopentanediformylimine and preparation method thereof Download PDFInfo
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- CN101235011A CN101235011A CNA2008100601281A CN200810060128A CN101235011A CN 101235011 A CN101235011 A CN 101235011A CN A2008100601281 A CNA2008100601281 A CN A2008100601281A CN 200810060128 A CN200810060128 A CN 200810060128A CN 101235011 A CN101235011 A CN 101235011A
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- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- 238000006243 chemical reaction Methods 0.000 claims abstract description 24
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 claims abstract description 18
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 claims abstract description 18
- 239000002904 solvent Substances 0.000 claims abstract description 18
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 claims abstract description 15
- 238000010992 reflux Methods 0.000 claims abstract description 13
- 238000001035 drying Methods 0.000 claims abstract description 6
- 239000002994 raw material Substances 0.000 claims abstract description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 23
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 21
- 235000019441 ethanol Nutrition 0.000 claims description 20
- 239000003960 organic solvent Substances 0.000 claims description 20
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 15
- 150000002148 esters Chemical class 0.000 claims description 14
- 125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 claims description 11
- 125000001142 dicarboxylic acid group Chemical group 0.000 claims description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical group CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 150000001298 alcohols Chemical class 0.000 claims description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 8
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 claims description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 6
- 239000011259 mixed solution Substances 0.000 claims description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 6
- 230000035484 reaction time Effects 0.000 claims description 5
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 claims description 4
- 239000007864 aqueous solution Substances 0.000 claims description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 3
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 claims description 3
- 150000005826 halohydrocarbons Chemical class 0.000 claims description 3
- 229930195733 hydrocarbon Natural products 0.000 claims description 3
- 150000002430 hydrocarbons Chemical class 0.000 claims description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical class CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 2
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 2
- 235000019445 benzyl alcohol Nutrition 0.000 claims description 2
- 229960004217 benzyl alcohol Drugs 0.000 claims description 2
- 229940043232 butyl acetate Drugs 0.000 claims description 2
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 claims description 2
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 claims description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims description 2
- NUKZAGXMHTUAFE-UHFFFAOYSA-N hexanoic acid methyl ester Natural products CCCCCC(=O)OC NUKZAGXMHTUAFE-UHFFFAOYSA-N 0.000 claims description 2
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 claims description 2
- 239000003921 oil Substances 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- BOVGTQGAOIONJV-BETUJISGSA-N 1-[(3ar,6as)-3,3a,4,5,6,6a-hexahydro-1h-cyclopenta[c]pyrrol-2-yl]-3-(4-methylphenyl)sulfonylurea Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1C[C@H]2CCC[C@H]2C1 BOVGTQGAOIONJV-BETUJISGSA-N 0.000 abstract description 12
- 229960000346 gliclazide Drugs 0.000 abstract description 12
- 239000002699 waste material Substances 0.000 abstract description 2
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 abstract 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 206010013786 Dry skin Diseases 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 230000002218 hypoglycaemic effect Effects 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- MQIUGAXCHLFZKX-UHFFFAOYSA-N Di-n-octyl phthalate Natural products CCCCCCCCOC(=O)C1=CC=CC=C1C(=O)OCCCCCCCC MQIUGAXCHLFZKX-UHFFFAOYSA-N 0.000 description 1
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 1
- 229910010082 LiAlH Inorganic materials 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 229940100389 Sulfonylurea Drugs 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 238000010923 batch production Methods 0.000 description 1
- 230000002902 bimodal effect Effects 0.000 description 1
- 150000001793 charged compounds Chemical class 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- -1 dioctyl phthalate imines Chemical group 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 150000002500 ions Chemical group 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 229940127017 oral antidiabetic Drugs 0.000 description 1
- 239000003538 oral antidiabetic agent Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Indole Compounds (AREA)
Abstract
The invention discloses an N-amino-1, 2-cyclopentane dicarboximide whose formula is represented as right. The invention also discloses a corresponding preparation method which comprises using cyclopentane ortho-anhydride as raw material, carrying out hydrazine hydrate in solvent for refluxing reaction for 0.5-12h while the mol ratio of cyclopentane ortho-anhydride and hydrazine hydrate is 1:1-2.5, removing solvent after reaction, and drying to obtain N-amino-1, 2-cyclopentane dicarboximide. The N-amino-1, 2-cyclopentane dicarboximide can be used as the intermediate of gliclazide, thereby reducing the reaction route of gliclazide to reduce waste.
Description
Technical field
The present invention relates to a kind of organism N-amino-1,2-cyclopentanediformylandne and chemical synthesis process thereof.
Background technology
N-amino-1,2-cyclopentanediformylandne are the key intermediates of preparation gliclazide (Gliclazide).Gliclazide is a s-generation sulfonylurea oral antidiabetic drug, has hypoglycemic and improves the dual function of coagulation function, is widely used clinically.The synthetic of gliclazide is raw material with the adjacent dioctyl phthalate imines of pentamethylene usually, in tetrahydrofuran (THF) with LiAlH
4The reaction, the reduction obtain heterocyclic (Griot, R.SiegfriedAkt.-Ges., Zofingen, Switz.Helvetica Chimica Acta.1959,42:67-72); This material is dissolved in the acetic acid with the Sodium Nitrite reaction obtains N-nitroso-group-3-azabicyclooctane, obtain six hydrogen-2-cyclopentano pyrryl amine (JP05065270A) through zinc powder reduction again, last and tolylsulfonylurea condensation obtains product (JP06041073A).Reaction process is as follows:
The main drawback of this reaction process is a complex steps, just can obtain product, the reaction cost height through the reaction of 4 steps.
Summary of the invention
The technical problem to be solved in the present invention provides a kind of N-amino-1,2-cyclopentanediformylandne and preparation method thereof, this N-amino-1, the 2-cyclopentanediformylandne can be as synthetic hypoglycemic drug---the intermediate of gliclazide, thereby shorten the reaction scheme of gliclazide, effectively reduce waste.
In order to solve the problems of the technologies described above, the invention provides a kind of N-amino-1, the 2-cyclopentanediformylandne, its chemical structural formula is:
The present invention also provides N-amino-1, the preparation method of 2-cyclopentanediformylandne is a raw material with the adjacent dicarboxylic acid anhydride of pentamethylene, carries out back flow reaction with hydrazine hydrate in solvent, reaction times is 0.5～12 hour, mol ratio=1: 1～2.5 of adjacent dicarboxylic acid anhydride of pentamethylene and hydrazine hydrate; Reaction removes solvent after finishing, and drying obtains N-amino-1, the 2-cyclopentanediformylandne.
Improvement as preparation method of the present invention: earlier the adjacent dicarboxylic acid anhydride of pentamethylene is put into solvent, then hydrazine hydrate is added in the solvent with the form that drips, described dropping is that normal temperature or reflux conditions drip down.
Further improvement as preparation method of the present invention: solvent is the mixed solution of mixed solution, other organic solvent except that alcohols and ester class and alcohol organic solvent of water, alcohol organic solvent, ester class organic solvent, other organic solvent except that alcohols and ester class and water or the mixed solution of other organic solvent except that alcohols and ester class and ester class organic solvent.Alcohol organic solvent is methyl alcohol, ethanol, propyl alcohol, Virahol, butanols, isopropylcarbinol, ethylene glycol, glycol ether, hexalin or benzylalcohol; Ester class organic solvent is ethyl acetate, methyl acetate or butylacetate.Other organic solvent except that alcohols and ester class is hydro carbons (for example being pentane, hexane, hexanaphthene, sherwood oil, benzene, toluene or dimethylbenzene), halohydrocarbon (chloroform, methylene dichloride or ethylene dichloride), acetone, butanone pimelinketone or tetrahydrofuran (THF).The mol ratio of the adjacent dicarboxylic acid anhydride of solvent and pentamethylene is 1～50: 1.
Further improvement as preparation method of the present invention: hydrazine hydrate is that massfraction is 25%～85% hydrazine hydrate aqueous solution.
Reaction equation of the present invention can be expressed as:
The product that adopts method preparation of the present invention has been determined the molecular ion peak of M=154 through gas phase-spectrometer analysis, and the succimide negative ion fragment of M=98.Through infrared analysis, at 1707cm
-1(charateristic avsorption band C=O) is at 3297cm the amidocarbonylation carbon-oxygen bond to have occurred
-1, 3174cm
-1(charateristic avsorption band N-H), and be bimodal proves primary amine the amino nitrogen hydrogen bond to have occurred.Finally be defined as N-amino-1, the 2-cyclopentanediformylandne.
With N-amino-1 of the present invention, the 2-cyclopentanediformylandne is used for the production gliclazide, and reaction process is as follows:
In sum, adopt N-amino-1 of the present invention, 2-cyclopentanediformylandne production gliclazide has shortened reactions steps, and helps environmental protection and reduce production costs; Be suitable for large-scale batch process.
Embodiment
Below in conjunction with specific embodiment the present invention is further described:
Embodiment 1: a kind of N-amino-1, the preparation method of 2-cyclopentanediformylandne, carry out following steps successively:
In reflux condensing tube, churned mechanically 250mL there-necked flask are housed, add the adjacent dicarboxylic acid anhydride of 14g pentamethylene, 50mL methyl alcohol, be heated to backflow after, slowly drip the hydrazine hydrate aqueous solution of 7mL 85%, dropwise the back and continued back flow reaction 6 hours.
After reaction finishes, stop heating, reaction solution to Rotary Evaporators place underpressure distillation is gone out solvent and water, obtain thick liquid, obtain product N-amino-1 after the cooling, the 2-cyclopentanediformylandne, in 30 ℃ of dryings 12 hours, obtain product 13.5g under the vacuum, yield is 87.7%.
Embodiment 2: a kind of N-amino-1, the preparation method of 2-cyclopentanediformylandne, carry out following steps successively:
In reflux condensing tube, churned mechanically 250mL there-necked flask are housed, add the adjacent dicarboxylic acid anhydride of 14g pentamethylene, 50mL methyl alcohol, normal temperature drip the hydrazine hydrate of 7mL 85% down, dropwise post-heating to refluxing 7 hours reaction times.
After reaction finishes, stop heating, reaction solution to Rotary Evaporators place underpressure distillation is gone out solvent and water, obtain thick liquid, obtain product N-amino-1 after the cooling, the 2-cyclopentanediformylandne, in 30 ℃ of dryings 12 hours, obtain product 13.2g under the vacuum, yield is 85.7%.
Embodiment 3～11: change solvent, hydrazine hydrate concentration and hydrazine hydrate consumption, reaction times in the foregoing description 1 or 2, can obtain respective embodiments 3～11.Particular content sees Table 1, and the product yield of each embodiment gained sees Table 1.
The concrete data of table 1, embodiment 3～11
| Embodiment | Raw material consumption g | Solvent and consumption mL | The concentration % of hydrazine hydrate aqueous solution and consumption ml | Hydrazine hydrate drips mode | Reaction times h | Yield % |
| 3 | 14 | Ethanol (100mL) | 80％，10ml | Reflux and drip | 7 | 82.6 |
| 4 | 20 | Water (60mL) | 85％，8ml | Normal temperature drips | 3 | 78.6 |
| 5 | 14 | Ethyl acetate (30mL), ethanol (50mL) | 65％，15ml | Reflux and drip | 6 | 76.4 |
| 6 | 20 | Methyl alcohol (120mL) | 25％，40ml | Normal temperature drips | 0.5 | 76.6 |
| 7 | 20 | Toluene (120mL) | 85％，22ml | Reflux and drip | 5 | 72.8 |
| 8 | 20 | Methyl alcohol (80mL), ethylene dichloride (20mL) | 85％，15ml | Normal temperature drips | 2 | 78.3 |
| 9 | 40 | Ethanol (250mL) | 45％，40ml | Normal temperature drips | 12 | 64.2 |
| 10 | 14 | Sherwood oil (60mL), methyl alcohol (60mL) | 85％，8ml | Reflux and drip | 6 | 82.4 |
| 11 | 14 | Glycol ether (80mL) | 85％，7ml | Reflux and drip | 4 | 79.2 |
Synthesizing of embodiment 12, six hydrogen-2-cyclopentano pyrryl amine:
In reflux condensing tube, churned mechanically 250mL there-necked flask are housed, add the 80mL tetrahydrofuran (THF), be preheated to and add the 25g aluminum chloride about 50 ℃, add the 12g POTASSIUM BOROHYDRIDE after stirring 10min, add 15.4gN-amino-1 behind the restir 15min, the 2-cyclopentanediformylandne is heated to backflow, reacts 7 hours.Reaction finishes postcooling, and with the extraction of 50 * 3mL toluene, extraction liquid adds hydrochloric acid, is acidified to pH ≈ 3, and underpressure distillation goes out toluene and less water, obtains the product hydrochloride, and uses ethyl alcohol recrystallization, obtains the hydrochloride 12.8g of product, and yield is 78.7%.
Synthesizing of embodiment 13, gliclazide:
In reflux condensing tube, churned mechanically 250mL there-necked flask are housed, add the hydrochloride of 16.3g six hydrogen-2-cyclopentano pyrryl amine, the 22g tolylsulfonylurea, 100mL DMF is heated to backflow, reacts about 2 hours.Reaction finishes to drip water 100mL, is cooled to about 10 ℃ and separates out material, filters, and an amount of washing obtains the product gliclazide.In 80 ℃ of dryings 12 hours, obtain product 28.2g under the vacuum, fusing point is 163.1～165.3 ℃, and yield is 87.2%.
At last, it is also to be noted that what more than enumerate only is several specific embodiments of the present invention.Obviously, the invention is not restricted to above embodiment, many distortion can also be arranged.All distortion that those of ordinary skill in the art can directly derive or associate from content disclosed by the invention all should be thought protection scope of the present invention.
Claims (9)
1, a kind of N-amino-1, the 2-cyclopentanediformylandne is characterized in that its chemical structural formula is:
2, as claim 1 described N-amino-1, the preparation method of 2-cyclopentanediformylandne, it is characterized in that: with the adjacent dicarboxylic acid anhydride of pentamethylene is raw material, in solvent, carry out back flow reaction with hydrazine hydrate, reaction times is 0.5～12 hour, mol ratio=1: 1～2.5 of adjacent dicarboxylic acid anhydride of pentamethylene and hydrazine hydrate; Reaction removes solvent after finishing, and drying obtains N-amino-1, the 2-cyclopentanediformylandne.
3, according to claim 2 described N-amino-1, the preparation method of 2-cyclopentanediformylandne, it is characterized in that: earlier the adjacent dicarboxylic acid anhydride of pentamethylene is put into solvent, then hydrazine hydrate is added in the solvent with the form that drips, described dropping is that normal temperature or reflux conditions drip down.
4, according to claim 2 or 3 described N-amino-1, the preparation method of 2-cyclopentanediformylandne is characterized in that: described solvent is the mixed solution of mixed solution, other organic solvent except that alcohols and ester class and alcohol organic solvent of water, alcohol organic solvent, ester class organic solvent, other organic solvent except that alcohols and ester class and water or the mixed solution of other organic solvent except that alcohols and ester class and ester class organic solvent.
5, according to claim 4 described N-amino-1, the preparation method of 2-cyclopentanediformylandne is characterized in that: described alcohol organic solvent is methyl alcohol, ethanol, propyl alcohol, Virahol, butanols, isopropylcarbinol, ethylene glycol, glycol ether, hexalin or benzylalcohol; Described ester class organic solvent is ethyl acetate, methyl acetate or butylacetate.
6, according to claim 5 described N-amino-1, the preparation method of 2-cyclopentanediformylandne is characterized in that: described other organic solvent except that alcohols and ester class is hydro carbons, halohydrocarbon, acetone, butanone pimelinketone or tetrahydrofuran (THF).
7, according to claim 6 described N-amino-1, the preparation method of 2-cyclopentanediformylandne, it is characterized in that: described hydro carbons is pentane, hexane, hexanaphthene, sherwood oil, benzene, toluene or dimethylbenzene, and described halohydrocarbon is chloroform, methylene dichloride or ethylene dichloride.
8, according to claim 7 described N-amino-1, the preparation method of 2-cyclopentanediformylandne is characterized in that: the mol ratio of the adjacent dicarboxylic acid anhydride of described solvent and pentamethylene is 1～50: 1.
9, according to claim 8 described N-amino-1, the preparation method of 2-cyclopentanediformylandne is characterized in that: described hydrazine hydrate is that massfraction is 25%～85% hydrazine hydrate aqueous solution.
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011054312A1 (en) * | 2009-11-09 | 2011-05-12 | 浙江九洲药业股份有限公司 | Method for preparing gliclazide and its intermediate |
| CN102382034A (en) * | 2010-09-06 | 2012-03-21 | 山东方明药业股份有限公司 | Synthetic method of N-amino-3-azabicyclo[3,3,0]octane hydrochloride |
| CN102584677A (en) * | 2012-02-07 | 2012-07-18 | 安徽金鼎医药有限公司 | Method for preparing gliclazide |
| CN102924362A (en) * | 2012-10-26 | 2013-02-13 | 浙江工业大学 | Preparation method of hexahydro-2-cyclopentyl-pyrryl amine hydrochloride |
| CN103183632A (en) * | 2011-12-29 | 2013-07-03 | 山东方明药业集团股份有限公司 | Purification method of 3-azabicyclo-octane hydrochloride |
| CN103601666A (en) * | 2013-11-28 | 2014-02-26 | 遵义医学院 | Preparation method of octahydrocyclopentane[C]pyrrole |
| CN106588746A (en) * | 2016-11-25 | 2017-04-26 | 盘锦格林凯默科技有限公司 | Preparation method of gliclazide side chain and preparation method of gliclazide |
| CN108084080A (en) * | 2018-01-22 | 2018-05-29 | 安徽金鼎医药股份有限公司 | A kind of preparation method of gliclazide intermediate hexahydro cyclopentano [c] pyrrole radicals -2- amine hydrochlorates |
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2008
- 2008-03-11 CN CN200810060128A patent/CN100591667C/en not_active Expired - Fee Related
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| CN102584677B (en) * | 2012-02-07 | 2014-01-08 | 安徽金鼎医药有限公司 | Method for preparing gliclazide |
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| CN103601666A (en) * | 2013-11-28 | 2014-02-26 | 遵义医学院 | Preparation method of octahydrocyclopentane[C]pyrrole |
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| CN106588746B (en) * | 2016-11-25 | 2019-08-13 | 盘锦格林凯默科技有限公司 | The preparation method of gliclazide side chain and the preparation method of gliclazide |
| CN108084080A (en) * | 2018-01-22 | 2018-05-29 | 安徽金鼎医药股份有限公司 | A kind of preparation method of gliclazide intermediate hexahydro cyclopentano [c] pyrrole radicals -2- amine hydrochlorates |
| CN110372568A (en) * | 2019-08-22 | 2019-10-25 | 山东海佑福瑞达制药有限公司 | A kind of crystallization and preparation method thereof of gliclazide intermediate |
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