CN107698491A - A kind of preparation method of substituted piperidine derivative - Google Patents
A kind of preparation method of substituted piperidine derivative Download PDFInfo
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- CN107698491A CN107698491A CN201610643008.9A CN201610643008A CN107698491A CN 107698491 A CN107698491 A CN 107698491A CN 201610643008 A CN201610643008 A CN 201610643008A CN 107698491 A CN107698491 A CN 107698491A
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- 150000003053 piperidines Chemical class 0.000 title claims abstract description 19
- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 13
- 238000003379 elimination reaction Methods 0.000 claims abstract description 12
- 238000009903 catalytic hydrogenation reaction Methods 0.000 claims abstract description 11
- 150000001875 compounds Chemical class 0.000 claims abstract description 10
- -1 (amino methyl) 4 iodobenzene epoxide Chemical class 0.000 claims abstract description 9
- 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
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 16
- 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
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 11
- 238000006146 oximation reaction Methods 0.000 claims description 9
- 238000006266 etherification reaction Methods 0.000 claims description 8
- WWKKTHALZAYYAI-UHFFFAOYSA-N 2-iodobenzaldehyde Chemical compound IC1=CC=CC=C1C=O WWKKTHALZAYYAI-UHFFFAOYSA-N 0.000 claims description 7
- 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
- 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
- 238000006243 chemical reaction Methods 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
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- XBXHCBLBYQEYTI-UHFFFAOYSA-N piperidin-4-ylmethanol Chemical class OCC1CCNCC1 XBXHCBLBYQEYTI-UHFFFAOYSA-N 0.000 claims description 3
- 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
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims 12
- 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
- URLKBWYHVLBVBO-UHFFFAOYSA-N Para-Xylene Chemical group CC1=CC=C(C)C=C1 URLKBWYHVLBVBO-UHFFFAOYSA-N 0.000 claims 8
- IVSZLXZYQVIEFR-UHFFFAOYSA-N m-xylene Chemical group CC1=CC=CC(C)=C1 IVSZLXZYQVIEFR-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
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims 6
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical group CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims 6
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims 6
- 238000000034 method Methods 0.000 claims 5
- 229910052757 nitrogen Inorganic materials 0.000 claims 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims 3
- 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 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims 3
- 229940113088 dimethylacetamide Drugs 0.000 claims 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims 2
- 229910019213 POCl3 Inorganic materials 0.000 claims 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims 2
- OHLUUHNLEMFGTQ-UHFFFAOYSA-N N-methylacetamide Chemical compound CNC(C)=O OHLUUHNLEMFGTQ-UHFFFAOYSA-N 0.000 claims 1
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims 1
- 229910000564 Raney nickel Inorganic materials 0.000 claims 1
- AFCIMSXHQSIHQW-UHFFFAOYSA-N [O].[P] Chemical compound [O].[P] AFCIMSXHQSIHQW-UHFFFAOYSA-N 0.000 claims 1
- 239000003054 catalyst Substances 0.000 claims 1
- 239000007795 chemical reaction product Substances 0.000 claims 1
- 235000019253 formic acid Nutrition 0.000 claims 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims 1
- RUPAXCPQAAOIPB-UHFFFAOYSA-N tert-butyl formate Chemical compound CC(C)(C)OC=O RUPAXCPQAAOIPB-UHFFFAOYSA-N 0.000 abstract description 3
- 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
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 abstract 1
- 229910052740 iodine Inorganic materials 0.000 abstract 1
- 239000011630 iodine Substances 0.000 abstract 1
- 238000003786 synthesis reaction Methods 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 6
- 238000000926 separation method Methods 0.000 description 4
- JDDAFHUEOVUDFJ-UHFFFAOYSA-N 2-iodobenzonitrile Chemical compound IC1=CC=CC=C1C#N JDDAFHUEOVUDFJ-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 238000006555 catalytic reaction Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 2,3-dimethylbutane Chemical group CC(C)C(C)C ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 0.000 description 1
- KQDJTBPASNJQFQ-UHFFFAOYSA-N 2-iodophenol Chemical class OC1=CC=CC=C1I KQDJTBPASNJQFQ-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000003810 ethyl acetate extraction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([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)
Abstract
The invention discloses a kind of preparation method of substituted piperidine derivative 4 ((2 (amino methyl) 4 iodobenzene epoxide) methyl) piperidinyl-1 t-butyl formate, using the hydroxy benzaldehyde of 5 iodine 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 substituted piperidine derivative 4-
The preparation method of ((2- (amino methyl) -4- iodobenzenes epoxide) methyl) piperidines -1- t-butyl formates.
Technical background
Compound 4- ((2- (amino methyl) -4- iodobenzenes epoxide) methyl) piperidines -1- t-butyl formates, structural formula are：
This compound 4- ((2- (amino methyl) -4- iodobenzenes epoxide) methyl) piperidines -1- t-butyl formates and correlation spread out
Biology has extensive use in pharmaceutical chemistry and organic synthesis.4- ((2- (amino methyl) -4- iodobenzenes epoxide) methyl) at present
The synthesis of piperidines -1- t-butyl formates is more difficult.Therefore it is easy to get, it is necessary to develop a raw material, easy to operate, reaction is easy to control
System, the suitable synthetic method of overall yield.
The content of the invention
The invention discloses a kind of substituted piperidine derivative 4- ((2- (amino methyl) -4- iodobenzenes epoxide) methyl) piperidines -
The preparation method of 1- t-butyl formates, using the iodo- Benzaldehyde,2-hydroxies of 5- as initiation material, by oximate, elimination, etherificate, catalysis
Hydrogenation reaction obtains target product 5, and synthesis step is as follows：
(1) using the iodo- Benzaldehyde,2-hydroxies of 5- 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；Used in described etherification reaction prepare compound 4
Reagent is selected from 4- (hydroxymethyl) piperidines -1- t-butyl formates；Catalysis used in described catalytic hydrogenation reaction prepare compound 5
Agent is selected from palladium carbon.
In a preferred embodiment, the solvent used in described oximation reaction prepare compound 2 is selected from ethanol；It is described
Elimination reaction prepare compound 3 used in solvent be selected from acetic anhydride；Solvent used in described etherification reaction prepare compound 4
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；Institute
The temperature used in elimination reaction prepare compound 3 stated is the reflux temperature of solvent；The described institute of etherification reaction prepare compound 4
Temperature is room temperature；Temperature used in described catalytic hydrogenation reaction prepare compound 5 is room temperature.
The present invention relates to a kind of substituted piperidine derivative 4- ((2- (amino methyl) -4- iodobenzenes epoxide) methyl) piperidines -1-
The preparation method of the preparation method of t-butyl formate, reported currently without other Patents documents.
The present invention is further described by the following embodiment, and these descriptions are not present invention to be made into one
The restriction of step.It should be understood by those skilled in the art that the equivalent substitution made to the technical characteristic of the present invention, or change accordingly
Enter, still fall within protection scope of the present invention.
Specific embodiment mode
Embodiment 1
(1) synthesis of the iodo- Benzaldehyde,2-hydroxy oximes of 5-
The iodo- Benzaldehyde,2-hydroxies of 30g 5- are added in 270ml ethanol, 17g hydroxylamine hydrochlorides is added dropwise to, was stirred at room temperature
At night, cooling, water and ethyl acetate are added, extract liquid separation, collect organic phase, dried, concentration, obtain the iodo- 2- hydroxy benzenes of 23g 5-
Formaldoxime.
(2) synthesis of the iodo- 2- hydroxy benzonitriles of 5-
The iodo- Benzaldehyde,2-hydroxy oximes of 23g 5- are added in 190ml acetic anhydride, are heated to reflux stirring 2 hours, are concentrated,
Residue is poured into frozen water, ethyl acetate extraction liquid separation is added, collects organic phase, dry, concentration, cross post separation and obtain
The iodo- 2- hydroxy benzonitriles of 16g5-.
(3) synthesis of 4- ((the iodo- 2- cyano-benzene oxygens of 4-) methyl) piperidines -1- t-butyl formates
The iodo- 2- hydroxy benzonitriles of 15g 5- 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, concentrates, it is remaining
Silica gel post separation obtains 17g 4- ((the iodo- 2- cyano-benzene oxygens of 4-) methyl) piperidines -1- t-butyl formates on thing.
(4) synthesis of 4- ((2- (amino methyl) -4- iodobenzenes epoxide) methyl) piperidines -1- t-butyl formates
17g 4- ((the iodo- 2- cyano-benzene oxygens of 4-) methyl) piperidines -1- t-butyl formates are added in 170ml methanol,
The palladium carbons of 1g 10% are added, leads to hydrogen, is stirred at room temperature 24 hours, are filtered, filtrate is collected, concentration, obtains 7g 4- ((2- (amino first
Base) -4- iodobenzenes epoxide) methyl) piperidines -1- t-butyl formates.
Claims (6)
1. a kind of substituted piperidine derivative 4- ((2- (amino methyl) -4- iodobenzenes epoxide) methyl) piperidines -1- t-butyl formates
Preparation method, using the iodo- Benzaldehyde,2-hydroxies of 5- 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 the iodo- Benzaldehyde,2-hydroxies of 5- 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. method according to claim 1, it is characterised in that 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 one or both of acetic anhydride, POCl3
Mixture；Reagent used in described etherification reaction prepare compound 4 is selected from the tertiary fourth of 4- (hydroxymethyl) piperidines -1- formic acid
Ester；The one kind of catalyst in palladium carbon, palladium dydroxide, Raney's nickel used in described catalytic hydrogenation reaction prepare compound 5
Or one or more of mixtures in several mixtures.
4. method according to claim 1, 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, meta-xylene, N,
One or more of mixtures in dinethylformamide, DMAC N,N' dimethyl acetamide, triethylamine, pyridine, acetonitrile, acetic acid；
Solvent used in described elimination reaction prepare compound 3 is selected from methanol, ethanol, normal propyl alcohol, isopropanol, acetic anhydride, trichlorine oxygen
Phosphorus, tetrahydrofuran, dichloromethane, toluene, ortho-xylene, paraxylene, meta-xylene, N,N-dimethylformamide, N, N- bis-
One or more of mixtures in methylacetamide, acetonitrile, water；Solvent used in described etherification reaction prepare compound 4
Selected from methanol, ethanol, normal propyl alcohol, isopropanol, tetrahydrofuran, dioxane, dichloromethane, chloroform, toluene, adjacent diformazan
One kind in benzene, paraxylene, meta-xylene, N,N-dimethylformamide, DMAC N,N' dimethyl acetamide, acetonitrile, POCl3
Or several mixture；Solvent used in described catalytic hydrogenation reaction prepare compound 5 is selected from methanol, ethanol, normal propyl alcohol, different
Propyl alcohol, tetrahydrofuran, dioxane, dichloromethane, chloroform, toluene, ortho-xylene, paraxylene, meta-xylene, N, N-
One or more of mixtures in dimethylformamide, DMAC N,N' dimethyl acetamide, acetic acid, water.
5. method according to claim 1, 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 temperature of 0 DEG C~solvent
Degree；Temperature used in described etherification reaction prepare compound 4 is the reflux temperature of 0 DEG C~solvent；Described catalytic hydrogenation is anti-
Answer the reflux temperature that the temperature used in prepare compound 5 is 0 DEG C~solvent.
6. method according to claim 1, 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；It is prepared by described etherification reaction
Temperature used in compound 4 is room temperature；Temperature used in described catalytic hydrogenation reaction prepare compound 5 is room temperature.
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| CN201610643008.9A CN107698491A (en) | 2016-08-08 | 2016-08-08 | A kind of preparation method of substituted piperidine derivative |
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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 |
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- 2016-08-08 CN CN201610643008.9A patent/CN107698491A/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 |
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