CN106478487B - Pyrrolidine compounds and synthesis method thereof - Google Patents
Pyrrolidine compounds and synthesis method thereof Download PDFInfo
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- CN106478487B CN106478487B CN201610831473.5A CN201610831473A CN106478487B CN 106478487 B CN106478487 B CN 106478487B CN 201610831473 A CN201610831473 A CN 201610831473A CN 106478487 B CN106478487 B CN 106478487B
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- benzyl
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- pyrrolidines
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- 150000003235 pyrrolidines Chemical class 0.000 title claims abstract description 14
- 238000001308 synthesis method Methods 0.000 title claims 2
- -1 pyrrolidine compound Chemical class 0.000 claims abstract description 21
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 17
- 239000001257 hydrogen Substances 0.000 claims abstract description 17
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000003638 chemical reducing agent Substances 0.000 claims abstract description 10
- 238000010992 reflux Methods 0.000 claims abstract description 8
- 125000003118 aryl group Chemical group 0.000 claims abstract description 6
- 239000003054 catalyst Substances 0.000 claims abstract description 4
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 11
- 238000006243 chemical reaction Methods 0.000 claims description 11
- 238000010189 synthetic method Methods 0.000 claims description 5
- KWEKXPWNFQBJAY-UHFFFAOYSA-N (dimethyl-$l^{3}-silanyl)oxy-dimethylsilicon Chemical compound C[Si](C)O[Si](C)C KWEKXPWNFQBJAY-UHFFFAOYSA-N 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- 239000012044 organic layer Substances 0.000 claims description 3
- FGTWRFGVFTTZOI-UHFFFAOYSA-N 2-benzyl-1,3-dihydroisoindole Chemical compound C1C2=CC=CC=C2CN1CC1=CC=CC=C1 FGTWRFGVFTTZOI-UHFFFAOYSA-N 0.000 claims description 2
- AFYZAHZKOFBVLE-UHFFFAOYSA-N 6-benzyl-1,2,3,4,4a,5,7,7a-octahydropyrrolo[3,4-b]pyridine Chemical compound C1C2CCCNC2CN1CC1=CC=CC=C1 AFYZAHZKOFBVLE-UHFFFAOYSA-N 0.000 claims description 2
- 238000004440 column chromatography Methods 0.000 claims description 2
- GWVMLCQWXVFZCN-UHFFFAOYSA-N isoindoline Chemical compound C1=CC=C2CNCC2=C1 GWVMLCQWXVFZCN-UHFFFAOYSA-N 0.000 claims description 2
- 238000010791 quenching Methods 0.000 claims description 2
- 229910052710 silicon Inorganic materials 0.000 abstract description 14
- 239000010703 silicon Substances 0.000 abstract description 14
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 abstract description 12
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 7
- 238000000034 method Methods 0.000 abstract description 4
- 239000002841 Lewis acid Substances 0.000 abstract description 3
- 150000007517 lewis acids Chemical class 0.000 abstract description 3
- 239000003960 organic solvent Substances 0.000 abstract description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 abstract 2
- 238000009776 industrial production Methods 0.000 abstract 1
- 230000002194 synthesizing effect Effects 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 32
- 150000001875 compounds Chemical class 0.000 description 16
- 238000003786 synthesis reaction Methods 0.000 description 11
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 8
- 238000005160 1H NMR spectroscopy Methods 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 4
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 229910052736 halogen Inorganic materials 0.000 description 3
- 150000002367 halogens Chemical class 0.000 description 3
- 150000003233 pyrroles Chemical class 0.000 description 3
- FNEQHKCQXDKYEO-UHFFFAOYSA-N 1-benzylpyrrole Chemical compound C1=CC=CN1CC1=CC=CC=C1 FNEQHKCQXDKYEO-UHFFFAOYSA-N 0.000 description 2
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 description 2
- 150000001336 alkenes Chemical class 0.000 description 2
- 125000000304 alkynyl group Chemical group 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 229910052796 boron Inorganic materials 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 125000004093 cyano group Chemical group *C#N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 150000003949 imides Chemical class 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- WYDUSKDSKCASEF-LJQANCHMSA-N (1s)-1-cyclohexyl-1-phenyl-3-pyrrolidin-1-ylpropan-1-ol Chemical compound C([C@](O)(C1CCCCC1)C=1C=CC=CC=1)CN1CCCC1 WYDUSKDSKCASEF-LJQANCHMSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical class ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- OXFMJRAOSJKURE-UHFFFAOYSA-N 2-benzyl-1,3,3a,4,5,6,7,7a-octahydroisoindole Chemical compound C1C2CCCCC2CN1CC1=CC=CC=C1 OXFMJRAOSJKURE-UHFFFAOYSA-N 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- PMRVFZXOCRHXFE-FMEJWYFOSA-L Kad 1229 Chemical compound [Ca+2].C([C@@H](CC(=O)N1C[C@@H]2CCCC[C@@H]2C1)C(=O)[O-])C1=CC=CC=C1.C([C@@H](CC(=O)N1C[C@@H]2CCCC[C@@H]2C1)C(=O)[O-])C1=CC=CC=C1 PMRVFZXOCRHXFE-FMEJWYFOSA-L 0.000 description 1
- WITXFYCLPDFRNM-UHFFFAOYSA-N N-Benzylphthalimide Chemical compound O=C1C2=CC=CC=C2C(=O)N1CC1=CC=CC=C1 WITXFYCLPDFRNM-UHFFFAOYSA-N 0.000 description 1
- GJWAPAVRQYYSTK-UHFFFAOYSA-N [(dimethyl-$l^{3}-silanyl)amino]-dimethylsilicon Chemical compound C[Si](C)N[Si](C)C GJWAPAVRQYYSTK-UHFFFAOYSA-N 0.000 description 1
- 238000007171 acid catalysis Methods 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 229910000085 borane Inorganic materials 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 150000001924 cycloalkanes Chemical class 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 238000006459 hydrosilylation reaction Methods 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 239000011968 lewis acid catalyst Substances 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229960003365 mitiglinide Drugs 0.000 description 1
- FABPRXSRWADJSP-MEDUHNTESA-N moxifloxacin Chemical compound COC1=C(N2C[C@H]3NCCC[C@H]3C2)C(F)=CC(C(C(C(O)=O)=C2)=O)=C1N2C1CC1 FABPRXSRWADJSP-MEDUHNTESA-N 0.000 description 1
- 229960003702 moxifloxacin Drugs 0.000 description 1
- 150000002790 naphthalenes Chemical class 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- UMRZSTCPUPJPOJ-KNVOCYPGSA-N norbornane Chemical compound C1C[C@H]2CC[C@@H]1C2 UMRZSTCPUPJPOJ-KNVOCYPGSA-N 0.000 description 1
- JFNLZVQOOSMTJK-KNVOCYPGSA-N norbornene Chemical compound C1[C@@H]2CC[C@H]1C=C2 JFNLZVQOOSMTJK-KNVOCYPGSA-N 0.000 description 1
- 125000000538 pentafluorophenyl group Chemical group FC1=C(F)C(F)=C(*)C(F)=C1F 0.000 description 1
- 229920001843 polymethylhydrosiloxane Polymers 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 229960005253 procyclidine Drugs 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 229920002545 silicone oil Polymers 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- UORVGPXVDQYIDP-UHFFFAOYSA-N trihydridoboron Substances B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/58—[b]- or [c]-condensed
- C07D209/62—Naphtho [c] pyrroles; Hydrogenated naphtho [c] pyrroles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/58—[b]- or [c]-condensed
- C07D209/72—4,7-Endo-alkylene-iso-indoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/02—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements
- C07D295/027—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring
- C07D295/03—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring with the ring nitrogen atoms directly attached to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Indole Compounds (AREA)
Abstract
一种吡咯烷类化合物及其合成方法，将溶解于有机溶剂中的环状酰亚胺类化合物与作为还原剂的硅氢试剂和作为催化剂的路易斯酸混合，在回流的条件下制备得到芳香环以及脂肪环吡咯烷类化合物。本发明合成路线简洁，高效和经济，条件温和，适用性广，对吡咯烷类化合物的后期工业化生产将起到极大的推动作用。A pyrrolidine compound and a method for synthesizing the same. The cyclic imide compound dissolved in an organic solvent is mixed with a silicon hydrogen reagent as a reducing agent and a Lewis acid as a catalyst, and an aromatic ring is prepared under reflux conditions. and alicyclic pyrrolidine compounds. The synthetic route of the invention is simple, efficient and economical, the conditions are mild, and the applicability is wide, which will greatly promote the later-stage industrial production of the pyrrolidine compounds.
Description
Technical field
The present invention relates to a kind of technology of chemical field, specifically a kind of Louis acid catalysis cyclic imide class
The silicon hydrogenation for closing object prepares the synthetic method of pyrrolidines.
Background technique
Pyrrolidines are one of heterocyclic compound important kinds, are prevalent in some natural products, medicine
Object intermediate, drug molecule, in functional material, thus the synthesis of pyrrolidines have in terms of organic synthesis it is important
Meaning.
It is most straightforward approach by restoring imide analog compounds come synthesis of pyrrolidine class compound, prepares pyrroles at present
The classical restoring method of alkyl compound is to use the compounds such as Lithium Aluminium Hydride, borine as reducing agent to realize.Due to acyl
There are multiple intermediates for the reduction of imine compound, and the formation of by-product, and this kind of reduction are caused using this kind of reducing agent
The functional group compatibility of reagent is poor.Simultaneously because the activity of reducing agent is higher, the disadvantages of to water sensitive, need the reaction usually
It is strict controlled in the environment of anhydrous and low temperature and carries out, and the post-processing step reacted is comparatively laborious.
Summary of the invention
The present invention In view of the above shortcomings of the prior art, proposes a kind of pyrrolidines and its synthetic method,
It is reducing agent, boron-containing compound as catalyst using the silicon hydrogen species compound of cheap and simple from imide analog compounds
Catalyzed hydrosilation restores cyclic imide class compound and realizes that synthetic route is succinct, mild condition, is suitable for large scale quantities
It produces.
The present invention is achieved by the following technical solutions:
The present invention relates to a kind of pyrrolidines, structural formulas are as follows:Or
Wherein:
R1For benzyl containing different substituents, alkane, alkene, alkynyl, aryl or contain all kinds of functional groups (cyano, halogen, carbonyl
Base, alkoxy, amino, hydroxyl) alkyl chain；
R2For halogen, alkoxy, carbonyl, naphthalene nucleus, amino or protection amino；
R3For benzyl containing different substituents, alkane, alkene, alkynyl, aryl or contain all kinds of functional groups (cyano, halogen, carbonyl
Base, alkoxy, amino, hydroxyl) alkyl chain；
R4For hydrogen, cycloalkane, norbornane, norbornene or hexahydropyridine.
The present invention relates to the synthetic method of above-mentioned pyrrolidines, the cyclic imide that will be dissolved in organic solvent
Class compound is mixed with the silicon hydrogen reagent as reducing agent and the lewis acid as catalyst, is prepared under conditions of reflux
It is as follows to aromatic rings and cycloaliphatic ring pyrrolidines, reaction equation:
The lewis acid is further preferred are as follows: three-(pentafluorophenyl group) boron, phenyl boric acid, substituted phenyl boric acid or trifluoro
Change borate ether etc..
The reducing agent is more preferably three silicon hydrogen of aryl, three silicon hydrogen of alkyl, diaryl silicon hydrogen, dialkyl group silicon hydrogen,
1,1,3,3- tetramethyl disiloxane, PMHS (containing hydrogen silicone oil) or triaryl silicon hydrogen etc..
The organic solvent is toluene, 1,4- dioxane, 1,2- dichloroethanes or chloroform.
The reaction molar ratio of the amount of hydrogen is 1/6-1/4, catalysis in the cyclic imide class compound and silicon hydrogen reagent
The dosage of agent is the 0.1-2.0mol% of cyclic imide.
The reflux refers to that water is added after the reaction was completed and quenches remaining silicon hydrogen examination for the back flow reaction under 110 DEG C of environment
Agent is concentrated after extracting organic layer, and direct column chromatographs to obtain target product.
The present invention relates to the applications for the pyrrolidines that the above method is prepared, will be in pyrrolidines
Manufacture of at least one compound for the important segment of Moxifloxacin, Mitiglinide Calcium and procyclidine etc..
Technical effect
Compared with prior art, the present invention with " highly selective " for background, using mild cheap reducing agent silicon hydrogen reagent,
In the presence of a lewis acid catalyst, preferably using common toluene as solvent, various substituted pyrroles are prepared in the case where reflux
Cough up alkyl compound.Compared to existing preparation process, reducing agent used in the present invention is easy to operate, and highly selective, substrate is suitable
Wide, the high income with property.
Specific embodiment
Embodiment 1
The present embodiment is related to N- benzyl isoindolineSynthesis, the specific steps of which are as follows:
It is added in reaction tube N- benzylphthalimide (237.3mg, 1.0mmol), B (C6F5)3(10.2mg,
2.0mol%), silicon hydrogen reagent TMDS (335.8mg, 2.5mmol) slowly is added in system after toluene (2mL) stirring and dissolving, it will
Reaction temperature rises to 110 DEG C of reflux.It has reacted and the remaining silicon hydrogen reagent of water quenching is added, be concentrated after extracting organic layer, direct column
Chromatography obtains target product, yield: 95%.1H NMR(400MHz,CDCl3)δ7.44–7.42(m,2H),7.38–7.34(m,
2H),7.31–7.26(m,1H),7.18(s,4H),3.94(s,4H),3.92(s,2H).13C NMR(100MHz,CDCl3)δ
140.3,139.2,128.89,128.5,127.2,126.7,122.4,60.4,59.0.
Embodiment 2
The present embodiment is related to N- ((4- trifluoromethyl) benzyl) isoindolineSynthesis, tool
Steps are as follows for body:
According to operation same as Example 1, target compound is obtained, yield: 90%.1H NMR(400MHz,CDCl3)δ
7.62–7.60(m,2H),7.55–7.53(m,2H),7.20(s,4H),3.97(s,2H),3.94(s,4H).13C NMR
(100MHz,CDCl3) δ 143.5,140.1,129.5 (q, J=32.1Hz), 129.0,126.9,125.5 (q, J=3.7Hz),
124.4 (q, J=270.1Hz), 122.5,59.9,59.1.
Embodiment 3
The present embodiment is related to 2,6- dibenzyl -1,2,3,5,6,7- hexahydrobenzene parallel connection pyrroles
Synthesis, the specific steps of which are as follows:
According to operation same as Example 1, target compound is obtained, yield: 90%.1H NMR(400MHz,CDCl3)δ
7.41–7.39(m,4H),7.36–7.32(m,4H),7.29–7.27(m,2H),6.97(s,2H),3.89(s,4H),3.87(s,
8H).13C NMR(100MHz,CDCl3)δ139.2,139.0,128.9,128.5,127.2,116.5,60.5,58.9.
Embodiment 4
The present embodiment is related to N- benzyl -2,3- dihydro-benzisoindolineSynthesis, tool
Steps are as follows for body:
According to operation same as Example 1, target compound is obtained, yield: 89%.1H NMR(400MHz,CDCl3)δ
7.81–7.79(m,2H),7.63(s,2H),7.49–7.39(m,6H),7.35–7.32(m,1H),4.06(s,4H),3.97(s,
2H).13C NMR(100MHz,CDCl3)δ139.4,139.1,133.1,129.0,128.5,127.8,127.3,125.4,
120.6,60.6,58.7.
Embodiment 5
The present embodiment is related to N- benzyl -4,7- endo-methylene group-hexahydroisoindolineSynthesis, tool
Steps are as follows for body:
According to operation same as Example 1, target compound is obtained, yield: 94%.1H NMR(400MHz,CDCl3)δ
7.36-7.28 (m, 4H), 7.24-7.21 (m, 1H), 3.52 (s, 2H), 2.76 (d, J=10.0Hz, 2H), 2.35-2.34 (m,
2H),2.11(s,2H),2.02–1.98(m,2H),1.77–1.75(m,2H),1.41–1.33(m,2H),1.26–1.24(m,
2H).13C NMR(100MHz,CDCl3)δ140.5,128.5,128.2,126.7,60.7,55.4,44.1,42.3,41.4,
24.1.
Embodiment 6
The present embodiment is related to N- benzyl hexahydroisoindolineSynthesis, the specific steps of which are as follows:
According to operation same as Example 1, target compound is obtained, yield: 90%.1H NMR(400MHz,CDCl3)δ
7.38–7.32(m,4H),7.29–7.24(m,1H),3.76(s,2H),2.83–2.79(m,2H),2.57–2.53(m,2H),
2.21–2.15(m,2H),1.60–1.46(m,6H),1.38–1.30(m,2H).13C NMR(100MHz,CDCl3)δ139.9,
128.8,128.3,126.9,61.4,58.4,37.3,27.0,23.0.
Embodiment 7
The present embodiment is related to N- benzyl-pyrrole alkaneSynthesis, the specific steps of which are as follows:
According to operation same as Example 1, target compound is obtained, yield: 82%.1H NMR(400MHz,CDCl3)δ
7.35–7.23(m,5H),3.65(s,2H),2.55–2.53(m,4H),1.82–1.78(m,4H).13C NMR(100MHz,
CDCl3)δ139.2,129.0,128.3,127.0,60.8,54.2,23.5.
Embodiment 8
The present embodiment is related to 6- benzyl octahydro pyrrolo- [3,4-B] pyridineSynthesis, it is specific
Steps are as follows:
According to operation same as Example 1, target compound is obtained, yield: 85%.1H NMR(400MHz,CDCl3)δ
7.34–7.29(m,4H),7.27–7.22(m,1H),3.82–3.69(m,2H),3.28–3.26(m,1H),3.04–3.00(m,
1H),2.87–2.84(m,1H),2.80–2.75(m,1H),2.71–2.55(m,3H),2.29–2.21(m,1H),1.69–1.64
(m,2H),1.52–1.43(m,2H).13C NMR(100MHz,CDCl3)δ139.0,128.7,128.2,126.9,60.5,
59.8,56.1,55.0,43.8,36.2,23.9,21.4.
Above-mentioned specific implementation can by those skilled in the art under the premise of without departing substantially from the principle of the invention and objective with difference
Mode carry out local directed complete set to it, protection scope of the present invention is subject to claims and not by above-mentioned specific implementation institute
Limit, each implementation within its scope is by the constraint of the present invention.
Claims (1)
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103772320A (en) * | 2013-12-24 | 2014-05-07 | 浙江海翔药业股份有限公司 | Method for synthesizing tertiary amine by using alpha-amino acid as raw material |
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|---|---|---|---|---|
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| CN103772320A (en) * | 2013-12-24 | 2014-05-07 | 浙江海翔药业股份有限公司 | Method for synthesizing tertiary amine by using alpha-amino acid as raw material |
Non-Patent Citations (6)
| Title |
|---|
| 1,2:3"",4"";4,5-benzene.《Helvetica Chimica Acta》.1947,第30卷第2035-2045页. |
| 806623-06-3;CAS;《STN-REGISTRY》;20050102 |
| Ruggli,P.et al..Heterocyclic nitrogen compounds. LXI.Dipyrrolino-3",4" |
| Selective Catalytic Monoreduction of Phthalimides and Imidazolidine-2,4-diones;Shoubhik Das,et al.;《Angew. Chem. Int. Ed.》;20110824;第50卷;9180-9184 |
| 莫西沙星的合成;刘明亮等;《中国医药工业杂志》;20041231;第35卷(第3期);第129,131页 |
| 顺式全氢异吲哚的合成;李海波等;《华西药学杂志》;20081231;第23卷(第1期);第20-22页 |
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