CN107286076A - A kind of preparation method of piperidines - Google Patents
A kind of preparation method of piperidines Download PDFInfo
- Publication number
- CN107286076A CN107286076A CN201610207517.7A CN201610207517A CN107286076A CN 107286076 A CN107286076 A CN 107286076A CN 201610207517 A CN201610207517 A CN 201610207517A CN 107286076 A CN107286076 A CN 107286076A
- Authority
- CN
- China
- Prior art keywords
- prepare compound
- reaction prepare
- reaction
- temperature
- solvent
- 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.)
- Withdrawn
Links
- 150000003053 piperidines Chemical class 0.000 title claims abstract description 18
- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- 238000003379 elimination reaction Methods 0.000 claims abstract description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 12
- 238000009903 catalytic hydrogenation reaction Methods 0.000 claims abstract description 10
- 150000001875 compounds Chemical class 0.000 claims abstract description 10
- 230000000977 initiatory effect Effects 0.000 claims abstract description 5
- 239000000463 material Substances 0.000 claims abstract description 5
- 230000008030 elimination Effects 0.000 claims abstract description 3
- -1 (amino methyl) 4 bromobenzene epoxide Chemical class 0.000 claims abstract 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 15
- 239000002904 solvent Substances 0.000 claims description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 11
- 238000006266 etherification reaction Methods 0.000 claims description 9
- 238000006146 oximation reaction Methods 0.000 claims description 9
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 claims description 8
- 229940125782 compound 2 Drugs 0.000 claims description 7
- 229940126214 compound 3 Drugs 0.000 claims description 7
- 229940125898 compound 5 Drugs 0.000 claims description 7
- 238000006243 chemical reaction Methods 0.000 claims description 6
- 239000003153 chemical reaction reagent Substances 0.000 claims description 6
- 238000010992 reflux Methods 0.000 claims description 6
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 claims description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 4
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- XBXHCBLBYQEYTI-UHFFFAOYSA-N piperidin-4-ylmethanol Chemical class OCC1CCNCC1 XBXHCBLBYQEYTI-UHFFFAOYSA-N 0.000 claims description 3
- 239000003054 catalyst Substances 0.000 claims description 2
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 claims description 2
- 229910052763 palladium Inorganic materials 0.000 claims description 2
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims 12
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical group CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims 8
- URLKBWYHVLBVBO-UHFFFAOYSA-N Para-Xylene Chemical group CC1=CC=C(C)C=C1 URLKBWYHVLBVBO-UHFFFAOYSA-N 0.000 claims 8
- 239000000203 mixture Substances 0.000 claims 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 6
- 238000000034 method Methods 0.000 claims 6
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims 4
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims 4
- MHABMANUFPZXEB-UHFFFAOYSA-N O-demethyl-aloesaponarin I Natural products O=C1C2=CC=CC(O)=C2C(=O)C2=C1C=C(O)C(C(O)=O)=C2C MHABMANUFPZXEB-UHFFFAOYSA-N 0.000 claims 4
- 229940113088 dimethylacetamide Drugs 0.000 claims 4
- IVSZLXZYQVIEFR-UHFFFAOYSA-N m-xylene Chemical group CC1=CC=CC(C)=C1 IVSZLXZYQVIEFR-UHFFFAOYSA-N 0.000 claims 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims 4
- 229910019213 POCl3 Inorganic materials 0.000 claims 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims 3
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims 2
- 238000006555 catalytic reaction Methods 0.000 claims 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims 1
- 241000790917 Dioxys <bee> Species 0.000 claims 1
- 239000007795 chemical reaction product Substances 0.000 claims 1
- 229910052759 nickel Inorganic materials 0.000 claims 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 2
- RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 abstract 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 abstract 1
- 229910052801 chlorine Inorganic materials 0.000 abstract 1
- 239000000460 chlorine Substances 0.000 abstract 1
- RUPAXCPQAAOIPB-UHFFFAOYSA-N tert-butyl formate Chemical compound CC(C)(C)OC=O RUPAXCPQAAOIPB-UHFFFAOYSA-N 0.000 abstract 1
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
- 0 *N1CCC(COc(cc2)c(CN)cc2Cl)CC1 Chemical compound *N1CCC(COc(cc2)c(CN)cc2Cl)CC1 0.000 description 2
- NHWQMJMIYICNBP-UHFFFAOYSA-N 2-chlorobenzonitrile Chemical compound ClC1=CC=CC=C1C#N NHWQMJMIYICNBP-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- VTWKXBJHBHYJBI-SOFGYWHQSA-N (ne)-n-benzylidenehydroxylamine Chemical compound O\N=C\C1=CC=CC=C1 VTWKXBJHBHYJBI-SOFGYWHQSA-N 0.000 description 1
- ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 2,3-dimethylbutane Chemical group CC(C)C(C)C ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 0.000 description 1
- XWQDMIXVAYAZGB-UHFFFAOYSA-N N#Cc1cc(Cl)ccc1O Chemical compound N#Cc1cc(Cl)ccc1O XWQDMIXVAYAZGB-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 238000003810 ethyl acetate extraction Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical class C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
- C07D211/22—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by oxygen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Hydrogenated Pyridines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a kind of preparation method of piperidines 4 ((2 (amino methyl) 4 bromobenzene epoxide) methyl) piperidinyl-1 t-butyl formate, using the hydroxy benzaldehyde of 5 chlorine 2 as initiation material, target product is obtained by oximate, elimination, etherificate, catalytic hydrogenation reaction, the compound is important medicine intermediate.
Description
Technical field
The present invention relates to a kind of novel processing step of medicine intermediate, more particularly to a kind of preparation method of piperidines 4- ((2- (amino methyl) -4- chlorophenoxies) methyl) piperidines -1- t-butyl formates.
Technical background
Compound 4- ((2- (amino methyl) -4- chlorophenoxies) methyl) piperidines -1- t-butyl formates, structural formula is：
This compound 4- ((2- (amino methyl) -4- chlorophenoxies) methyl) piperidines -1- t-butyl formates and the derivative of correlation have extensive use in pharmaceutical chemistry and organic synthesis.The synthesis of current 4- ((2- (amino methyl) -4- chlorophenoxies) methyl) piperidines -1- t-butyl formates is more difficult.It is easy to get accordingly, it would be desirable to develop a raw material, it is easy to operate, react easily controllable, the suitable synthetic method of overall yield.
The content of the invention
The invention discloses a kind of preparation method of piperidines 4- ((2- (amino methyl) -4- chlorophenoxies) methyl) piperidines -1- t-butyl formates, using 5- chlorine-2-hydroxyls benzaldehyde as initiation material, target product 5 is obtained by oximate, elimination, etherificate, catalytic hydrogenation reaction, synthesis step is as follows：
(1) using 5- chlorine-2-hydroxyls benzaldehyde as initiation material, 2 are obtained by oximation reaction；
2) elimination reaction is carried out 2, obtains 3；
(3) 3 progress etherification reactions are obtained 4；
(4) 4 progress catalytic hydrogenation reactions are obtained 5；
In a preferred embodiment, the reagent used in described oximation reaction prepare compound 2 is selected from hydroxylamine hydrochloride；Reagent used in described elimination reaction prepare compound 3 is selected from acetic anhydride；Reagent used in described etherification reaction prepare compound 4 is selected from 4- (hydroxymethyl) piperidines -1- t-butyl formates；Catalyst used in described catalytic hydrogenation reaction prepare compound 5 is selected from palladium carbon.
In a preferred embodiment, the solvent used in described oximation reaction prepare compound 2 is selected from ethanol；Solvent used in described elimination reaction prepare compound 3 is selected from acetic anhydride；Solvent used in described etherification reaction prepare compound 4 is selected from tetrahydrofuran；Solvent used in described catalytic hydrogenation reaction prepare compound 5 is selected from methanol.
In a preferred embodiment, the reaction temperature used in described oximation reaction prepare compound 2 is room temperature；Temperature used in described elimination reaction prepare compound 3 is the reflux temperature of solvent；Temperature used in described etherification reaction prepare compound 4 is room temperature；Temperature used in described catalytic hydrogenation reaction prepare compound 5 is room temperature.
The present invention relates to a kind of preparation method of the preparation method of piperidines 4- ((2- (amino methyl) -4- chlorophenoxies) methyl) piperidines -1- t-butyl formates, reported currently without other Patents documents.
The present invention is further described by the following embodiment, and these descriptions are not that present invention is further limited.It should be understood by those skilled in the art that the equivalent substitution made to the technical characteristic of the present invention, or be correspondingly improved, still fall within protection scope of the present invention.
Specific embodiment mode
Embodiment 1
(1) synthesis of 5- chlorine-2-hydroxyls benzaldoxime
30g 5- chlorine-2-hydroxyl benzaldehydes are added in 270ml ethanol, 17g hydroxylamine hydrochlorides is added dropwise to, is stirred overnight at room temperature, are cooled down, water and ethyl acetate is added, extraction point liquid is collected organic phase, dried, and concentration obtains 23g 5- chlorine-2-hydroxyl benzaldoximes.
(2) synthesis of 5- chlorine-2-hydroxyls benzonitrile
23g 5- chlorine-2-hydroxyl benzaldoximes are added in 190ml acetic anhydride, stirring 2 hours is heated to reflux, concentration pours into residue in frozen water, ethyl acetate extraction point liquid is added, collects organic phase, dry, concentration crosses post separation and obtains 16g5- chlorine-2-hydroxyl benzonitriles.
(3) synthesis of 4- ((the chloro- 2- cyano-benzene oxygens of 4-) methyl) piperidines -1- t-butyl formates
15g 5- chlorine-2-hydroxyl benzonitriles are added in 180ml tetrahydrofurans, sequentially add 19g 4- (hydroxymethyl) piperidines -1- t-butyl formates, 42g triphenylphosphines, 35g diisopropyl azodiformates, it is stirred at room temperature 24 hours, silica gel post separation obtains 17g 4- ((the chloro- 2- cyano-benzene oxygens of 4-) methyl) piperidines -1- t-butyl formates on concentration, residue.
(4) synthesis of 4- ((2- (amino methyl) -4- chlorophenoxies) methyl) piperidines -1- t-butyl formates
17g 5- (1- benzyls -1,2,3,6- tetrahydropyridine -4- bases) -2- methylpyrimidines are added in 170ml methanol, add the palladium carbons of 1g 10%, logical hydrogen, it is stirred at room temperature 24 hours, filters, collects filtrate, concentration, obtains 7g 4- ((2- (amino methyl) -4- chlorophenoxies) methyl) piperidines -1- t-butyl formates.
Claims (6)
1. a kind of preparation of piperidines 4- ((2- (amino methyl) -4- bromobenzenes epoxide) methyl) piperidines -1- t-butyl formates
Method, using 5- chlorine-2-hydroxyls benzaldehyde as initiation material, mesh is obtained by oximate, elimination, etherificate, catalytic hydrogenation reaction
Product 5 is marked, synthetic route is as follows,
2. method according to claim 1, it is characterized in that described 4 steps reaction is,
(1) using 5- chlorine-2-hydroxyls benzaldehyde as initiation material, 2 are obtained by oximation reaction；
(2) elimination reaction is carried out 2, obtains 3；
(3) 3 progress etherification reactions are obtained 4；
(4) 4 progress catalytic hydrogenation reactions are obtained 5；
3. according to claim 1-2 method, it is characterised in that the reagent used in described oximation reaction prepare compound 2 is selected from
Hydroxylamine hydrochloride；One kind in acetic anhydride, POCl3 of reagent used in described elimination reaction prepare compound 3 or
Two kinds of mixture；Reagent used in described etherification reaction prepare compound 4 is selected from 4- (hydroxymethyl) piperidines -1-
T-butyl formate；Catalyst used in described catalytic hydrogenation reaction prepare compound 5 is selected from palladium carbon, palladium dydroxide, thunder
One or more of mixtures in one or more of mixtures in Buddhist nun's nickel.
4. according to claim 1-2 method, it is characterised in that the solvent used in described oximation reaction prepare compound 2 is selected from
Methanol, ethanol, normal propyl alcohol, isopropanol, tetrahydrofuran, dichloromethane, toluene, ortho-xylene, paraxylene,
One kind in dimethylbenzene, N,N-dimethylformamide, DMAC N,N' dimethyl acetamide, triethylamine, pyridine, acetonitrile, acetic acid
Or several mixtures；Solvent used in described elimination reaction prepare compound 3 be selected from methanol, ethanol, normal propyl alcohol,
Isopropanol, acetic anhydride, POCl3, tetrahydrofuran, dichloromethane, toluene, ortho-xylene, paraxylene, two
One or more of mixtures in toluene, N,N-dimethylformamide, DMAC N,N' dimethyl acetamide, acetonitrile, water；Institute
The solvent used in etherification reaction prepare compound 4 stated be selected from methanol, ethanol, normal propyl alcohol, isopropanol, tetrahydrofuran,
Dioxane, dichloromethane, chloroform, toluene, ortho-xylene, paraxylene, meta-xylene, N, N- dimethyl
One or more of mixtures in formamide, DMAC N,N' dimethyl acetamide, acetonitrile, POCl3；Described catalysis adds
Solvent used in hydrogen reaction prepare compound 5 is selected from methanol, ethanol, normal propyl alcohol, isopropanol, tetrahydrofuran, dioxy six
Ring, dichloromethane, chloroform, toluene, ortho-xylene, paraxylene, meta-xylene, N,N-dimethylformamide,
One or more of mixtures in DMAC N,N' dimethyl acetamide, acetic acid, water.
5. according to claim 1-2 method, it is characterised in that the reaction temperature used in described oximation reaction prepare compound 2
It is the reflux temperature of 0 DEG C~solvent；Temperature used in described elimination reaction prepare compound 3 is the backflow of 0 DEG C~solvent
Temperature；Temperature used in described etherification reaction prepare compound 4 is the reflux temperature of 0 DEG C~solvent；Described catalysis adds
Temperature used in hydrogen reaction prepare compound 5 is the reflux temperature of 0 DEG C~solvent.
6. according to claim 1-2 method, it is characterised in that the reaction temperature used in described oximation reaction prepare compound 2
It is room temperature；Temperature used in described elimination reaction prepare compound 3 is the reflux temperature of solvent；Described etherification reaction
Temperature used in prepare compound 4 is room temperature；Temperature used in described catalytic hydrogenation reaction prepare compound 5 is room temperature.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610207517.7A CN107286076A (en) | 2016-04-05 | 2016-04-05 | A kind of preparation method of piperidines |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610207517.7A CN107286076A (en) | 2016-04-05 | 2016-04-05 | A kind of preparation method of piperidines |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107286076A true CN107286076A (en) | 2017-10-24 |
Family
ID=60095699
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610207517.7A Withdrawn CN107286076A (en) | 2016-04-05 | 2016-04-05 | A kind of preparation method of piperidines |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107286076A (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103930416A (en) * | 2011-09-09 | 2014-07-16 | 默克专利股份公司 | Benzonitrile derivatives as kinase inhibitors |
-
2016
- 2016-04-05 CN CN201610207517.7A patent/CN107286076A/en not_active Withdrawn
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103930416A (en) * | 2011-09-09 | 2014-07-16 | 默克专利股份公司 | Benzonitrile derivatives as kinase inhibitors |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108863845B (en) | Preparation method of trifloxystrobin and intermediate thereof | |
| CN105646416B (en) | A kind of method that 2,3 dihydro-benzofuran derivatives are synthesized by palladium chtalyst | |
| CN104817515A (en) | Preparation method of benzene substituent oxadiazole compound | |
| EP3201171B1 (en) | Method of preparing intermediate of salmeterol | |
| CN104591959B (en) | A kind of preparation method of stilbene compound | |
| CN107286076A (en) | A kind of preparation method of piperidines | |
| CN106810513A (en) | A kind of preparation method of bridged piperazine derivatives | |
| CN103288708B (en) | The preparation method of 1- aryl -2- indolinone derivative | |
| CN108117510A (en) | A kind of preparation method of piperidine derivative | |
| CN107698491A (en) | A kind of preparation method of substituted piperidine derivative | |
| CN105461617A (en) | Preparation method for 4-[4-(trifluoromethoxy)phenoxyl]piperidine | |
| CN107778215A (en) | A kind of preparation method of fluorine substituted piperidine derivative | |
| CN107778216A (en) | A kind of preparation method of fluorine substituted piperidine derivative | |
| CN108610309A (en) | A kind of preparation method of piperidine derivative | |
| CN110028409B (en) | Polysubstituted naphthalene derivative and preparation method thereof | |
| CN106854174A (en) | A kind of preparation method of 4 substituted piperidine derivatives | |
| CN107400082A (en) | A kind of preparation method of substituted piperidine derivative | |
| CN107400099A (en) | The preparation method of Yi Zhong oxadiazole compounds | |
| CN107698547A (en) | A kind of preparation method of pyran derivate | |
| Mohareb et al. | Synthesis of novel tryptophan derivatives of potential biological activity | |
| CN107176949A (en) | A kind of preparation method of triazole pyrans hydrochloride | |
| CN105801508B (en) | The preparation method of SC 69124 | |
| DK3077355T3 (en) | NEW PROCEDURE FOR SYNTHESIS OF 7-METHOXY-NAPTHALEN-1-CARBALDEHYDE AND ITS USE IN THE SYNTHESIS OF AGOMELATIN | |
| CN104341389A (en) | Method for preparing triazolylpiperidine hydrochloride | |
| CN107033105A (en) | A kind of preparation method of morpholino ethylamine hydrochloride |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20171024 |
|
| WW01 | Invention patent application withdrawn after publication |