CN105753682A - Preparation method of cyclopentyl phenyl ketone - Google Patents
Preparation method of cyclopentyl phenyl ketone Download PDFInfo
- Publication number
- CN105753682A CN105753682A CN201610130276.0A CN201610130276A CN105753682A CN 105753682 A CN105753682 A CN 105753682A CN 201610130276 A CN201610130276 A CN 201610130276A CN 105753682 A CN105753682 A CN 105753682A
- Authority
- CN
- China
- Prior art keywords
- preparation
- ketone
- cyclopenta
- phenylcyclopentyl
- phenylcyclopentyl ketone
- 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.)
- Granted
Links
- VYDIMQRLNMMJBW-UHFFFAOYSA-N cyclopentyl(phenyl)methanone Chemical compound C=1C=CC=CC=1C(=O)C1CCCC1 VYDIMQRLNMMJBW-UHFFFAOYSA-N 0.000 title claims abstract description 52
- 238000002360 preparation method Methods 0.000 title claims abstract description 31
- 239000002904 solvent Substances 0.000 claims abstract description 27
- -1 2-cyclopentyl methyl Chemical group 0.000 claims abstract description 17
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 24
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 12
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 12
- WRGLZAJBHUOPFO-UHFFFAOYSA-N methyl 3-oxo-3-phenylpropanoate Chemical compound COC(=O)CC(=O)C1=CC=CC=C1 WRGLZAJBHUOPFO-UHFFFAOYSA-N 0.000 claims description 11
- GKKZMYDNDDMXSE-UHFFFAOYSA-N Ethyl 3-oxo-3-phenylpropanoate Chemical compound CCOC(=O)CC(=O)C1=CC=CC=C1 GKKZMYDNDDMXSE-UHFFFAOYSA-N 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 8
- 239000003513 alkali Substances 0.000 claims description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 6
- 239000002585 base Substances 0.000 claims description 5
- 230000007062 hydrolysis Effects 0.000 claims description 5
- 238000006460 hydrolysis reaction Methods 0.000 claims description 5
- 230000035484 reaction time Effects 0.000 claims description 5
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 4
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 3
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 3
- 239000002994 raw material Substances 0.000 abstract description 8
- 238000003912 environmental pollution Methods 0.000 abstract description 4
- JTRRORMZRSPHME-UHFFFAOYSA-N cyclopentyl 3-oxo-3-phenylpropanoate Chemical compound C(C1=CC=CC=C1)(=O)CC(=O)OC1CCCC1 JTRRORMZRSPHME-UHFFFAOYSA-N 0.000 abstract 2
- 230000003301 hydrolyzing effect Effects 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 72
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
- 239000012074 organic phase Substances 0.000 description 22
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 12
- 238000004440 column chromatography Methods 0.000 description 12
- 239000003480 eluent Substances 0.000 description 12
- 239000000376 reactant Substances 0.000 description 12
- 230000002829 reductive effect Effects 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 10
- CSNNHWWHGAXBCP-UHFFFAOYSA-L magnesium sulphate Substances [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- 239000003208 petroleum Substances 0.000 description 10
- 238000004519 manufacturing process Methods 0.000 description 9
- 238000000034 method Methods 0.000 description 8
- 238000006555 catalytic reaction Methods 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 231100000419 toxicity Toxicity 0.000 description 5
- 230000001988 toxicity Effects 0.000 description 5
- 239000002253 acid Substances 0.000 description 4
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium chloride Substances Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 4
- JBDSSBMEKXHSJF-UHFFFAOYSA-N cyclopentanecarboxylic acid Chemical compound OC(=O)C1CCCC1 JBDSSBMEKXHSJF-UHFFFAOYSA-N 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 150000002576 ketones Chemical class 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- JMANVNJQNLATNU-UHFFFAOYSA-N oxalonitrile Chemical compound N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- 238000003747 Grignard reaction Methods 0.000 description 3
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical class [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 3
- WGLPBDUCMAPZCE-UHFFFAOYSA-N Trioxochromium Chemical compound O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 230000007613 environmental effect Effects 0.000 description 3
- LBAQSKZHMLAFHH-UHFFFAOYSA-N ethoxyethane;hydron;chloride Chemical compound Cl.CCOCC LBAQSKZHMLAFHH-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N hydrochloric acid Substances Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 238000010189 synthetic method Methods 0.000 description 3
- 239000011701 zinc Substances 0.000 description 3
- ROUYUBHVBIKMQO-UHFFFAOYSA-N 1,4-diiodobutane Chemical compound ICCCCI ROUYUBHVBIKMQO-UHFFFAOYSA-N 0.000 description 2
- DDTVVMRZNVIVQM-UHFFFAOYSA-N 2-(1-azabicyclo[2.2.2]octan-3-yloxy)-1-cyclopentyl-1-phenylethanol;hydrochloride Chemical compound Cl.C1N(CC2)CCC2C1OCC(O)(C=1C=CC=CC=1)C1CCCC1 DDTVVMRZNVIVQM-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 102000003914 Cholinesterases Human genes 0.000 description 2
- 108090000322 Cholinesterases Proteins 0.000 description 2
- 238000005863 Friedel-Crafts acylation reaction Methods 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 238000006859 Swern oxidation reaction Methods 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 2
- NQZFAUXPNWSLBI-UHFFFAOYSA-N carbon monoxide;ruthenium Chemical compound [Ru].[Ru].[Ru].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-] NQZFAUXPNWSLBI-UHFFFAOYSA-N 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 229940048961 cholinesterase Drugs 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 2
- 238000006880 cross-coupling reaction Methods 0.000 description 2
- LPIQUOYDBNQMRZ-UHFFFAOYSA-N cyclopentene Chemical compound C1CC=CC1 LPIQUOYDBNQMRZ-UHFFFAOYSA-N 0.000 description 2
- 238000006114 decarboxylation reaction Methods 0.000 description 2
- LSXWFXONGKSEMY-UHFFFAOYSA-N di-tert-butyl peroxide Chemical compound CC(C)(C)OOC(C)(C)C LSXWFXONGKSEMY-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 229910001385 heavy metal Inorganic materials 0.000 description 2
- 238000009776 industrial production Methods 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 238000011031 large-scale manufacturing process Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 2
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 2
- RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 2
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 2
- 231100000572 poisoning Toxicity 0.000 description 2
- 230000000607 poisoning effect Effects 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 229910004373 HOAc Inorganic materials 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 229910021551 Vanadium(III) chloride Inorganic materials 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- BRTFVKHPEHKBQF-UHFFFAOYSA-N bromocyclopentane Chemical compound BrC1CCCC1 BRTFVKHPEHKBQF-UHFFFAOYSA-N 0.000 description 1
- 239000003183 carcinogenic agent Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000003153 cholinolytic effect Effects 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- CLRHEGMAWYPMJF-UHFFFAOYSA-N ethyl 2-oxo-3-phenylpropanoate Chemical compound CCOC(=O)C(=O)CC1=CC=CC=C1 CLRHEGMAWYPMJF-UHFFFAOYSA-N 0.000 description 1
- GFAUNYMRSKVDJL-UHFFFAOYSA-N formyl chloride Chemical compound ClC=O GFAUNYMRSKVDJL-UHFFFAOYSA-N 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000000762 glandular Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 231100000086 high toxicity Toxicity 0.000 description 1
- 125000001967 indiganyl group Chemical group [H][In]([H])[*] 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- OTCKOJUMXQWKQG-UHFFFAOYSA-L magnesium bromide Chemical compound [Mg+2].[Br-].[Br-] OTCKOJUMXQWKQG-UHFFFAOYSA-L 0.000 description 1
- 229910001623 magnesium bromide Inorganic materials 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N mandelic acid Chemical compound OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- KAOSFPBSWNREAY-UHFFFAOYSA-N methyl 2-oxo-3-phenylpropanoate Chemical class COC(=O)C(=O)CC1=CC=CC=C1 KAOSFPBSWNREAY-UHFFFAOYSA-N 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007833 oxidative deamination reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 229960003424 phenylacetic acid Drugs 0.000 description 1
- 239000003279 phenylacetic acid Substances 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
- 239000010970 precious metal Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000006462 rearrangement reaction Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 210000003079 salivary gland Anatomy 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 150000003333 secondary alcohols Chemical class 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 235000002639 sodium chloride Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- IPSRAFUHLHIWAR-UHFFFAOYSA-N zinc;ethane Chemical compound [Zn+2].[CH2-]C.[CH2-]C IPSRAFUHLHIWAR-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/673—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by change of size of the carbon skeleton
- C07C45/676—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by change of size of the carbon skeleton by elimination of carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/09—Preparation of carboxylic acids or their salts, halides or anhydrides from carboxylic acid esters or lactones
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a preparation method of cyclopentyl phenyl ketone.The preparation method includes hydrolyzing 2-cyclopentyl benzoylacetate as a raw material in basic solvents to obtain a product, namely the cyclopentyl phenyl ketone, wherein the 2-cyclopentyl benzoylacetate is 2-cyclopentyl methyl benzoylacetate or 2-cyclopentyl ethyl benzoylacetate.The preparation method of the cyclopentyl phenyl ketone has the advantages of environment-friendly solvents, little environmental pollution, easiness in operation, high yield, short technological period and low preparation cost.
Description
Technical field
The invention belongs to pharmaceutical technology field, be specifically related to the high efficiency preparation method of a kind of amyl ethyl quin ether hydrochloride key intermediate phenylcyclopentyl ketone.
Background technology
Amyl ethyl quin ether hydrochloride (penehyclidine hydrochloride, PCHE) be new cholinolytic a kind new medicine, be mainly used in preanesthetic medication with suppression salivary gland and air flue glandular secretion, organophosphorus poison (agricultural chemicals) poisoning first-aid treatment and poisoning the later stage or cholinesterase (ChE) aging after maintain atropinization.
Phenylcyclopentyl ketone is the key intermediate of synthetic hydrochloric acid amyl ethyl quin ether, and structure is as follows:
Existing synthetic technology has:
1, Tetrahedron Letters, the synthetic method of 2006,47,7749-7753 reports:
This route generates cyclopenta titanate esters at low temperatures with titanate esters and cyclopenta magnesium chloride, is subsequently adding benzene first cyanogen, H3O+I.e. can get phenylcyclopentyl ketone, yield is only 10%.
The limitation of this route is that reaction, with titanate esters as catalyst, uses the catalytic addition reaction of RMgBr to need anhydrous and oxygen-free condition, severe reaction conditions, and yield to be only 10%, is not suitable for industrial mass production.It addition, the benzene first cyanogen toxicity used is the biggest, the post processing of catalyst Ti acid esters enters water body, can cause certain environmental hazard.
2, Tetrahedron, 2003,59,6393-6402, Angew.Chem.Int.Ed.2014,53,8416-8420 and J.Org.Chem.1996,61, the 2726-2730 synthetic routes reported respectively are as follows:
Tetrahedron, the method for 2003,59,6393-6402 reports, with cyclopenta formyl chloride with bromobenzene RMgBr at-78 DEG C, VCl3Under catalysis, synthesis of phenyl cyclopenta ketone.Angew.Chem.Int.Ed.2014, the methods of 53,8416-8420 reports, with cyclopenta magnesium bromide as RMgBr and CO2Produce aryl acid, removing CO2, then forming two lithium intermediates with aryl lithium, then i.e. can get phenylcyclopentyl ketone with HCl cancellation reaction, yield is 65%.J.Org.Chem.1996, the benzoyl being catalyzed with CuCN of 61,2726-2730 reports and the coupling reaction of bromocyclopentane organic zinc reagent, yield is 84%.
The limitation of above-mentioned route is all to use RMgBr or organic zinc synthesis of phenyl cyclopenta ketone, must carry out anhydrous and oxygen-free operation at low temperature-78 DEG C or-45 DEG C, and not only low temperature energy consumption is high, and operating condition is harsh, is not suitable for industrialization large-scale production.It addition, catalyst CuCN and VCl used by Fan Ying3Toxicity is bigger, expensive, adds production cost undoubtedly, it is difficult to realize industrialized production.
3, Tetrahedron Letters.2002,43,8355-8357 and J.Am.Chem.Soc.1950,72,4823-4824 reports following route respectively:
This route is with cyclopenta phenmethylol through Swern oxidation reaction, and reaction is reacted 2 hours at-78 DEG C, and yield is (X=Br) 89% or (X=Cl) 90% or through CrO3/ HOAc oxidation obtains cyclopentyl phenyl ketone.
The limitation of this route is that reaction raw materials is generally synthesized by grignard reaction, is difficult to obtain.This reaction need to be carried out at low temperature-78 DEG C, and CrO3Have high toxicity to aquatile, for carcinogenic substance, tool corrosivity, excitant, operating condition is harsher.
4, J.Am.Chem.Soc.1969,91,462-467, Eur.J.Med.Chem.2001, the synthetic route of 36,265-286 and J.Med.Chem.2003,46,5512-5532 reports is as follows:
This route is with cyclopentanecarboxylic acid as initiation material, through chloride, AlCl3Catalysis or the Friedel Crafts acylation reaction of phosphoric acid catalyzed, can be with synthesis of phenyl cyclopenta ketone, total recovery 56%.
The limitation of this route is with cyclopentanecarboxylic acid as initiation material, costly, and its chloride, AlCl3The Friedel Crafts acylation reaction of catalysis is required to use that toxicity is relatively big, anhydrous benzene is solvent, operates harsher.It addition, course of reaction inevitably results from a large amount of HCl gas, metal Al residual, to producing, equipment requirement is higher and environment all can cause certain pollution.
5, the Ru of J.Org.Chem.1990,55,1286-1291 report3(CO)12The benzaldehyde of catalysis reacts with the reductive acylation of cyclopentene, Tetrahedron, the Cp of 2004,60,1339-1344 reports2ZrHCl/CBAN mediation 1, the cyclisation oxidation reaction of single silyl enol ether of 6-diene, J.Org.Chem.2008, Furukawa reagent E t of 73,3516-3522 reports2ZnCH2I or Et2The rearrangement reaction of Zn catalysis β-bromine season alcohol, Org.Lett.2011, the Pd (OAc) of 13,2062-2064 reports2The decarboxylation of the alpha-oxo-carboxyl acid of catalysis and aromatic yl acid salt cross-coupling reaction, J.Org.Chem.2014, the Cu (OAc) of 79,1867-1871 reports2/O2The oxidative deamination reaction of catalysis phenylacetic acid or Alpha-hydroxy phenylacetic acid, J.Am.Chem.Soc.2005, the concrete route of isomerization reaction of the allyl alcohol that the Cp*Ru (PN) of 127,6172-6173 reports is catalyzed is as follows:
The limitation of above route is that reaction employs noble metal such as Ru3(CO)12、Pd(OAc)2, Cu (OAc), Cp*Ru (PN) etc., expensive starting materials and easily cause heavy-metal residual.Some routes need to be at high temperature (200 DEG C), high pressure (20kg/cm-2CO) carrying out under, to producing, equipment requirement is higher, adds production cost undoubtedly；Portion of reagent (Et2ZnCH2I or Et2Zn) easily meet water acutely hydrolyze even occur burning or blast, be difficult to store, operation inconvenience；Cp2ZrHCl、ArBF3K price is costly, toxicity is relatively big and need to keep in Dark Place, and oxidant CBAN toxicity is relatively large, a certain degree of pollution can be caused to be not suitable for industrialized production environment.
6, J.Org.Chem.2015,80, Fan Xuesen et al. reports the free radical cross-coupling reaction of benzaldehyde that the tert-butyl peroxide (TBP) of microwave radiation technology is catalyzed and pentamethylene, and reaction obtains phenylcyclopentyl ketone with the yield of 56%, and yield is medium.Concrete route is as follows:
This route, can be with the synthesis of phenyl cyclopenta ketone of moderate yield with cheap benzene feedstock formaldehyde, but this route need to be at nitrogen (N2) protection, microwave radiation technology, operation more difficulty, be not suitable for industrial production and reaction need under high temperature (180 DEG C) react, industrial production cost is higher, be difficult to amplify produce.
In sum, being limited in that in existing document report synthesis route: RMgBr will be used to prepare secondary alcohol or directly prepare phenylcyclopentyl ketone, and reaction need to be carried out at low temperature-78 DEG C, and condition is the harshest；Use metal (AlCl3、Ru3(CO)12、Pd(OAc)2, Cu (OAc), Cp*Ru (PN)) method that is catalyzed, raw material sources itself need the harsh conditions such as grignard reaction to prepare, and product inevitably produces heavy-metal residual simultaneously.HTHP is the highest to the requirement of equipment, and cost is significantly increased, and catalyst itself is expensive, toxicity is relatively big, be difficult to storage etc..
Summary of the invention
Deficiency for above existing technique, the invention provides the preparation method of a kind of phenylcyclopentyl ketone, with the easy 2-cyclopenta Benzoylacetic acid ester prepared as raw material, in the solvent of alkaline matter, the de-ester group of hydrolysis, uses the solvent of environmental protection, and environmental pollution is little, processing ease, yield is high, and process cycle is short, and production cost is low.
The present invention, in order to realize foregoing invention purpose, adopts the following technical scheme that
A kind of preparation method of phenylcyclopentyl ketone, it is characterised in that: in the presence of a base, 2-cyclopenta Benzoylacetic acid ester is hydrolyzed into the decarboxylation under heating state of carboxyl, carboxyl in a solvent and i.e. obtains the phenylcyclopentyl ketone of rock-steady structure；Described 2-cyclopenta Benzoylacetic acid ester is 2-cyclopenta methyl benzoylacetate or 2-cyclopenta ethyl benzoylacetate.
2-cyclopenta Benzoylacetic acid ester of the present invention is 1:1.5-1:3.0 with the mol ratio of alkali, can effectively shorten the reaction time, improves reaction yield, reduces alkali and the consumption of solvent.
The temperature of hydrolysis of the present invention is 60-100 DEG C, and the reaction time is 3-10h.Preferably, temperature is 80-100 DEG C, and the reaction time is 5-8h.
Solvent of the present invention is the mixing of one or more in water, N,N-dimethylformamide, dimethyl sulfoxide and toluene.
Preferably, described solvent is water, for environmentally friendly solvent, it is to avoid use the environmental pollution that a large amount of organic solvent causes, and reduces production cost.
Alkali of the present invention is the mixing of one or more in NaOH, potassium hydroxide, caustic alcohol, sodium carbonate, potassium carbonate and cesium carbonate.
Preferably, described alkali is NaOH or potassium hydroxide.
Present invention firstly discloses the synthetic method that a kind of amyl ethyl quin ether hydrochloride key intermediate phenylcyclopentyl ketone is the most succinct.With 2-cyclopenta Benzoylacetic acid ester as raw material, in the solvent of alkaline matter, the de-ester group of hydrolysis, obtains phenylcyclopentyl ketone with high yield.
In the technical scheme of existing document report, synthetic method many employings grignard reaction of phenylcyclopentyl ketone or the method for precious metal catalyst obtain, and manufacturing cost is high, severe reaction conditions.The invention provides a kind of method that high yield prepares phenylcyclopentyl ketone, selecting 2-cyclopenta Benzoylacetic acid ester is raw material, the easily operation of process route safety, using the solvent of environmental protection, environmental pollution is little, easily operates, raw material is easy to get, and production cost is low, is suitable for industrialization large-scale production.
Detailed description of the invention
The present invention is further illustrated the most by way of example, provides the implementation detail of the present invention, but is not intended to limit protection scope of the present invention.
Preparing of raw material 2-cyclopenta methyl benzoylacetate of the present invention and 2-cyclopenta benzoyl acetic acid methyl ethyl ester is as follows:
The preparation of 2-cyclopenta methyl benzoylacetate
Take 1,4-bis-iodobutane (17.1g, 55mmol), sodium carbonate (35g, 330mmol) with phenylpyruvic acid methyl esters (9.80g, 55mmol) it is dissolved in 150ml DMF, stir 12 hours under conditions of 55-60 DEG C, being poured in ice by reactant mixture, and extract with 120ml ethyl acetate, organic phase anhydrous sodium sulfate concentrates after drying, crude by column chromatography purifies, eluant, eluent (n-hexane: ethyl acetate=9:1), obtains colourless liquid 5.74g, is 2-cyclopenta methyl benzoylacetate.
The preparation of 2-cyclopenta ethyl benzoylacetate
Take 1,4-bis-iodobutane (17.1g, 55mmol), sodium carbonate (35g, 330mmol) with phenylpyruvic acid ethyl ester (10.6g, 55mmol) it is dissolved in 170ml DMF, stir 12 hours under conditions of 55-60 DEG C, being poured in ice by reactant mixture, and extract with 100ml ethyl acetate, organic phase anhydrous sodium sulfate concentrates after drying, crude by column chromatography purifies, eluant, eluent (n-hexane: ethyl acetate=9:1), obtains colourless liquid 7.9g, is 2-cyclopenta ethyl benzoylacetate.
Embodiment 1
The preparation method of a kind of phenylcyclopentyl ketone, in the presence of a base, 2-cyclopenta methyl benzoylacetate hydrolyzes in a solvent, obtains product phenylcyclopentyl ketone.
Embodiment 2
The preparation method of a kind of phenylcyclopentyl ketone, in the presence of a base, 2-cyclopenta ethyl benzoylacetate hydrolyzes in a solvent, obtains product phenylcyclopentyl ketone.
Embodiment 3
The preparation of phenylcyclopentyl ketone
In 100ml round-bottomed flask, by 2-cyclopenta methyl benzoylacetate (10.0g, 43.05mmol, 1.0eq), caustic alcohol (5.86g, 86.10mmol, 2.0eq), it is suspended in 50.0mL dimethyl sulfoxide, it is warmed up to 95 DEG C react 8 hours, obtains product phenylcyclopentyl ketone.
Embodiment 4
The present embodiment is substantially the same manner as Example 3, on this basis:
Purify: reactant liquor is cooled to room temperature, add 50mL water, extract 3 times with ethyl acetate 20mL；Organic phase saturated sodium-chloride washs, and merges organic phase and uses anhydrous MgSO4Being dried, then remove solvent under reduced pressure, obtain thick product, column chromatography purifies, and eluant, eluent is ethyl acetate: petroleum ether (1:10), obtains 5.83g target product, yield 77.73%.
Embodiment 5
The preparation of phenylcyclopentyl ketone
In 100ml round-bottomed flask, by 2-cyclopenta methyl benzoylacetate (10.0g, 43.05mmol, 1.0eq), K2CO3(11.90g, 86.10mmol, 2.0eq), is suspended in 50.0mL DMF, is warmed up to 60 DEG C and reacts 6 hours, obtains product phenylcyclopentyl ketone.
Embodiment 6
The present embodiment is substantially the same manner as Example 5, on this basis:
Purify: reactant liquor is cooled to room temperature, add 50mL water, extract 3 times with ethyl acetate 20mL；Organic phase saturated sodium-chloride washs, and merges organic phase and uses anhydrous MgSO4Being dried, then remove solvent under reduced pressure, obtain thick product, column chromatography purifies, and eluant, eluent is ethyl acetate: petroleum ether (1:10), obtains 5.23g target product, yield 69.73%.
Embodiment 7
The preparation of phenylcyclopentyl ketone
In 100ml round-bottomed flask, 2-cyclopenta methyl benzoylacetate (10.0g, 43.05mmol, 1.0eq), NaOH (2.58g, 64.57mmol, 1.5eq) are suspended in 80.0mL H2In O, it is warmed up to 95 DEG C and reacts 10 hours, obtain product phenylcyclopentyl ketone.
Purify: reactant liquor is cooled to room temperature, extract 3 times with ethyl acetate 20mL；Organic phase saturated sodium-chloride washs, and merges organic phase and uses anhydrous MgSO4Being dried, then remove solvent under reduced pressure, obtain thick product, column chromatography purifies, and eluant, eluent is ethyl acetate: petroleum ether (1:10), obtains 5.95g target product, yield 79.33%.
Embodiment 8
The preparation of phenylcyclopentyl ketone
In 100ml round-bottomed flask, by 2-cyclopenta methyl benzoylacetate (10.0g, 43.05mmol, 1.0eq), KOH (4.83g, 86.10mmol, 2.0eq), it is suspended in 50.0mLH2In O, it is warmed up to 80 DEG C and reacts 6 hours, obtain product phenylcyclopentyl ketone.
Purify: reactant liquor is cooled to room temperature, extract 3 times with ethyl acetate 20mL；Organic phase saturated sodium-chloride washs, and merges organic phase and uses anhydrous MgSO4Being dried, then remove solvent under reduced pressure, obtain thick product, column chromatography purifies, and eluant, eluent is ethyl acetate: petroleum ether (1:10), obtains 6.13g target product, yield 81.73%.
Embodiment 9
The preparation of phenylcyclopentyl ketone
In 100ml round-bottomed flask, by 2-cyclopenta methyl benzoylacetate (10.0g, 43.05mmol, 1.0eq), KOH (2.4g, 43mmol) and K2CO3(5.95g, 43mmol), is suspended in 50.0mLH2In O, it is warmed up to 80 DEG C and reacts 6 hours, obtain product phenylcyclopentyl ketone.
Purify: reactant liquor is cooled to room temperature, extract 3 times with ethyl acetate 20mL；Organic phase saturated sodium-chloride washs, and merges organic phase and uses anhydrous MgSO4Being dried, then remove solvent under reduced pressure, obtain thick product, column chromatography purifies, and eluant, eluent is ethyl acetate: petroleum ether (1:10), obtains 6.74g target product, yield 89.83%.
Embodiment 10
The preparation of phenylcyclopentyl ketone
In 100ml round-bottomed flask, by 2-cyclopenta ethyl benzoylacetate (10.6g, 43.05mmol, 1.0eq), NaOH (3.445g, 86.10mmol, 2.0eq), it is suspended in 25.0mLH2In O and 25mLDMF mixed solvent, it is warmed up to 100 DEG C and reacts 5 hours, obtain product phenylcyclopentyl ketone.
Embodiment 11
The present embodiment is substantially the same manner as Example 10, on this basis:
Purify: reactant liquor is cooled to room temperature, add 20mL water, extract 3 times with ethyl acetate 20mL；Organic phase saturated sodium-chloride washs, and merges organic phase and uses anhydrous MgSO4Being dried, then remove solvent under reduced pressure, obtain thick product, column chromatography purifies, and eluant, eluent is ethyl acetate: petroleum ether (1:10), obtains 6.02g target product, yield 80.26%.
Embodiment 12
The preparation of phenylcyclopentyl ketone
In 100ml round-bottomed flask, by 2-cyclopenta ethyl benzoylacetate (10.6g, 43.05mmol, 1.0eq), Na2CO3(9.12g, 86.10mmol, 2.0eq), is suspended in 25.0mLH2In O and 25.0mL dimethyl sulfoxide mixed solvent, it is warmed up to 100 DEG C and reacts 6 hours, obtain product phenylcyclopentyl ketone.
Purify: reactant liquor is cooled to room temperature, add 20mL water, extract 3 times with ethyl acetate 20mL；Organic phase saturated sodium-chloride washs, and merges organic phase and uses anhydrous MgSO4Being dried, then remove solvent under reduced pressure, obtain thick product, column chromatography purifies, and eluant, eluent is ethyl acetate: petroleum ether (1:10), obtains 6.0g target product, yield 80.0%.
Embodiment 13
The preparation of phenylcyclopentyl ketone
In 100ml round-bottomed flask, by 2-cyclopenta ethyl benzoylacetate (10.6g, 43.05mmol, 1.0eq), NaOH (5.17g, 129.15mmol, 3.0eq), it is suspended in 50.0mLH2In O, it is warmed up to 80 DEG C and reacts 3 hours, obtain product phenylcyclopentyl ketone.
Purify: reactant liquor is cooled to room temperature, extract 3 times with ethyl acetate 20mL；Organic phase saturated sodium-chloride washs, and merges organic phase and uses anhydrous MgSO4Being dried, then remove solvent under reduced pressure, obtain thick product, column chromatography purifies, and eluant, eluent is ethyl acetate: petroleum ether (1:10), obtains 6.23g target product, yield 83.06%.
Embodiment 14
The preparation of phenylcyclopentyl ketone
In 100ml round-bottomed flask, by 2-cyclopenta ethyl benzoylacetate (10.6g, 43.05mmol, 1.0eq), Cs2CO3(42.07g, 129.15mmol, 3.0eq), is suspended in 50.0mLH2In O, it is warmed up to 80 DEG C and reacts 3 hours, obtain product phenylcyclopentyl ketone.
Purify: reactant liquor is cooled to room temperature, extract 3 times with ethyl acetate 20mL；Organic phase saturated sodium-chloride washs, and merges organic phase and uses anhydrous MgSO4Being dried, then remove solvent under reduced pressure, obtain thick product, column chromatography purifies, and eluant, eluent is ethyl acetate: petroleum ether (1:10), obtains 3.45g target product, yield 46.0%.
Embodiment 15
The preparation of phenylcyclopentyl ketone
In 100ml round-bottomed flask, by 2-cyclopenta ethyl benzoylacetate (10.6g, 43.05mmol, 1.0eq), NaOH (2.6g, 64.5mmol) and Na2CO3(4.5g, 43mmol), is suspended in 50.0mLH2In O, it is warmed up to 80 DEG C and reacts 3 hours, obtain product phenylcyclopentyl ketone.
Purify: reactant liquor is cooled to room temperature, extract 3 times with ethyl acetate 20mL；Organic phase saturated sodium-chloride washs, and merges organic phase and uses anhydrous MgSO4Being dried, then remove solvent under reduced pressure, obtain thick product, column chromatography purifies, and eluant, eluent is ethyl acetate: petroleum ether (1:10), obtains 6.54g target product, yield 87.2%.
Claims (8)
1. the preparation method of a phenylcyclopentyl ketone, it is characterised in that: in the presence of a base, 2-ring penta
Base Benzoylacetic acid ester hydrolyzes in a solvent, obtains product phenylcyclopentyl ketone；Described 2-cyclopenta
Benzoylacetic acid ester is 2-cyclopenta methyl benzoylacetate or 2-cyclopenta ethyl benzoylacetate.
The preparation method of a kind of phenylcyclopentyl ketone the most according to claim 1, it is characterised in that: described
The mol ratio of 2-cyclopenta Benzoylacetic acid ester and alkali be 1:1.5-1:3.0.
The preparation method of a kind of phenylcyclopentyl ketone the most according to claim 1, it is characterised in that: described
The temperature of hydrolysis is 60-100 DEG C, and the reaction time is 3-10h.
The preparation method of a kind of phenylcyclopentyl ketone the most according to claim 3, it is characterised in that: described
The temperature of hydrolysis is 80-100 DEG C, and the reaction time is 5-8h.
The preparation method of a kind of phenylcyclopentyl ketone the most according to claim 1, it is characterised in that: described
Solvent be the mixing of one or more in water, N,N-dimethylformamide, dimethyl sulfoxide and toluene.
The preparation method of a kind of phenylcyclopentyl ketone the most according to claim 5, it is characterised in that: described
Solvent be water.
The preparation method of a kind of phenylcyclopentyl ketone the most according to claim 1, it is characterised in that: described
Alkali be the one in NaOH, potassium hydroxide, caustic alcohol, sodium carbonate, potassium carbonate and cesium carbonate or
Multiple mixing.
The preparation method of a kind of phenylcyclopentyl ketone the most according to claim 7, it is characterised in that: described
Alkali be NaOH or potassium hydroxide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610130276.0A CN105753682B (en) | 2016-03-08 | 2016-03-08 | A kind of preparation method of phenylcyclopentyl ketone |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610130276.0A CN105753682B (en) | 2016-03-08 | 2016-03-08 | A kind of preparation method of phenylcyclopentyl ketone |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105753682A true CN105753682A (en) | 2016-07-13 |
| CN105753682B CN105753682B (en) | 2018-01-09 |
Family
ID=56332842
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610130276.0A Active CN105753682B (en) | 2016-03-08 | 2016-03-08 | A kind of preparation method of phenylcyclopentyl ketone |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105753682B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107337595A (en) * | 2017-07-12 | 2017-11-10 | 海门华祥医药科技有限公司 | Synthetic process of cyclopentyl phenyl ketone |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2012056876A (en) * | 2010-09-08 | 2012-03-22 | Jx Nippon Oil & Energy Corp | Dicarbonyl compound, intermediate thereof, and method for producing the same |
| CN102548951A (en) * | 2009-07-24 | 2012-07-04 | 帝斯曼医药化学雷根斯堡技术有限公司 | Indane derivatives for use as intermediates |
| CN104321311A (en) * | 2012-05-22 | 2015-01-28 | 埃科特莱茵药品有限公司 | New process for the preparation of 2-cyclopentyl-6-methoxy-isonicotinic acid |
-
2016
- 2016-03-08 CN CN201610130276.0A patent/CN105753682B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102548951A (en) * | 2009-07-24 | 2012-07-04 | 帝斯曼医药化学雷根斯堡技术有限公司 | Indane derivatives for use as intermediates |
| JP2012056876A (en) * | 2010-09-08 | 2012-03-22 | Jx Nippon Oil & Energy Corp | Dicarbonyl compound, intermediate thereof, and method for producing the same |
| CN104321311A (en) * | 2012-05-22 | 2015-01-28 | 埃科特莱茵药品有限公司 | New process for the preparation of 2-cyclopentyl-6-methoxy-isonicotinic acid |
Non-Patent Citations (2)
| Title |
|---|
| GRZEGORZ KRZYSZTOF ZIELIŃSKI等: "In tandem or alone: a remarkably selective transfer hydrogenation of alkenes catalyzed by ruthenium olefin metathesis catalysts", 《ORG. BIOMOL. CHEM.》 * |
| JUN QIN等: "Stereocontrol in hydride addition to ketone-derived chiral N-acylhydrazones", 《TETRAHEDRON》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107337595A (en) * | 2017-07-12 | 2017-11-10 | 海门华祥医药科技有限公司 | Synthetic process of cyclopentyl phenyl ketone |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105753682B (en) | 2018-01-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Chen et al. | A practical palladium catalyzed dehalogenation of aryl halides and α-haloketones | |
| Choi et al. | Tin-or titanium-catalyzed dimethyl carbonate synthesis from carbon dioxide and methanol: large promotion by a small amount of triflate salts | |
| EP2562152B1 (en) | A method for preparing 2,5-dimethylphenylacetic acid | |
| Choshi et al. | Total syntheses of carazostatin and hyellazole by allene-mediated electrocyclic reaction | |
| Zheng et al. | Controlled Ni-catalyzed mono-and double-decarbonylations of α-ketothioesters | |
| CN107602372B (en) | Method for preparing fatty acid | |
| CN105693470A (en) | Continuous 3-methyl-3-buten-1-ol production method | |
| CN111777477B (en) | Method for synthesizing succinic acid derivative or 3-aryl propionic acid | |
| Shi et al. | Nickel catalyzed reduction of arenols under mild conditions | |
| CN109438234A (en) | A kind of synthetic method of the fluoro- 4- methoxy benzyl alcohol of 2,3,5,6- tetra- | |
| Luo et al. | Base-mediated carboxylation of C-nucleophiles with CO 2 | |
| Wang et al. | One-pot synthesis of 2-aryl-3-alkoxycarbonyl chromones through a cascade Lewis acid-catalyzed aldehyde olefination/oxa-Michael addition/oxidation | |
| CN101381338A (en) | The preparation method of cis-perhydroisoindole | |
| CN105753682B (en) | A kind of preparation method of phenylcyclopentyl ketone | |
| Chaudhari et al. | Intrinsic catalytic activity of Brønsted acid ionic liquids for the synthesis of triphenylmethane and phthalein under microwave irradiation | |
| RU2404173C2 (en) | Method for synthesis of methyl ether of 5-acetylfuran-2-carboxylic acid | |
| CN105198707B (en) | The synthetic method of 4 biphenylmethanols | |
| CN103159776B (en) | The total synthesis method of a kind of natural active product hypoxylonin and analogue thereof | |
| Hang et al. | Reaction of difluorocarbene with propargyl esters and efficient synthesis of difluorocyclopropyl ketones | |
| WO2018236218A1 (en) | Production and use of furan compounds | |
| CN105330633A (en) | Preparation method for biphenyltetracarboxylic dianhydride mixture | |
| Zhang et al. | Valorization of poly (butylene succinate) to tetrahydrofuran via one-pot catalytic hydrogenolysis | |
| CN102336656B (en) | High-selectivity synthesis method of benzoyl formic acid | |
| CN105348037A (en) | Synthetic method of directly coupling aryl halide by aromatic hydrocarbon Grignard reagent in the presence of recycled modified palladium-charcoal | |
| Yao et al. | A practical approach to stereodefined cyclopropyl-substituted heteroarenes using a Suzuki-type reaction |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |