CN110317132A - A kind of preparation method of phenylbutyrate sodium - Google Patents
A kind of preparation method of phenylbutyrate sodium Download PDFInfo
- Publication number
- CN110317132A CN110317132A CN201910681637.4A CN201910681637A CN110317132A CN 110317132 A CN110317132 A CN 110317132A CN 201910681637 A CN201910681637 A CN 201910681637A CN 110317132 A CN110317132 A CN 110317132A
- Authority
- CN
- China
- Prior art keywords
- reaction
- compound
- added
- preparation
- vacuum distillation
- 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
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- RHLFTMGPBSLHRS-UHFFFAOYSA-M sodium;2-phenylbutanoate Chemical compound [Na+].CCC(C([O-])=O)C1=CC=CC=C1 RHLFTMGPBSLHRS-UHFFFAOYSA-M 0.000 title 1
- 238000006243 chemical reaction Methods 0.000 claims abstract description 30
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 24
- VPZRWNZGLKXFOE-UHFFFAOYSA-M sodium phenylbutyrate Chemical compound [Na+].[O-]C(=O)CCCC1=CC=CC=C1 VPZRWNZGLKXFOE-UHFFFAOYSA-M 0.000 claims abstract description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 15
- MLIREBYILWEBDM-UHFFFAOYSA-N cyanoacetic acid Chemical compound OC(=O)CC#N MLIREBYILWEBDM-UHFFFAOYSA-N 0.000 claims abstract description 14
- 150000001875 compounds Chemical class 0.000 claims abstract description 13
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 claims abstract description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 11
- 239000000463 material Substances 0.000 claims abstract description 10
- 239000007795 chemical reaction product Substances 0.000 claims abstract description 9
- 238000005292 vacuum distillation Methods 0.000 claims abstract description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 8
- 229940058934 aminoquinoline antimalarials Drugs 0.000 claims abstract description 8
- 150000005010 aminoquinolines Chemical class 0.000 claims abstract description 8
- 239000000741 silica gel Substances 0.000 claims abstract description 8
- 229910002027 silica gel Inorganic materials 0.000 claims abstract description 8
- 239000002904 solvent Substances 0.000 claims abstract description 8
- LHDWRNHALCCNAR-UHFFFAOYSA-N C1CCC(CC1)OP(=O)(C2=CC=CN2C3=CC=CC=C3)OC4CCCCC4 Chemical class C1CCC(CC1)OP(=O)(C2=CC=CN2C3=CC=CC=C3)OC4CCCCC4 LHDWRNHALCCNAR-UHFFFAOYSA-N 0.000 claims abstract description 7
- 238000005660 chlorination reaction Methods 0.000 claims abstract description 7
- 239000000539 dimer Substances 0.000 claims abstract description 7
- XIXADJRWDQXREU-UHFFFAOYSA-M lithium acetate Chemical compound [Li+].CC([O-])=O XIXADJRWDQXREU-UHFFFAOYSA-M 0.000 claims abstract description 7
- 239000012298 atmosphere Substances 0.000 claims abstract description 6
- OWBTYPJTUOEWEK-UHFFFAOYSA-N butane-2,3-diol Chemical compound CC(O)C(C)O OWBTYPJTUOEWEK-UHFFFAOYSA-N 0.000 claims abstract description 5
- 238000000605 extraction Methods 0.000 claims abstract description 5
- 229940057372 buphenyl Drugs 0.000 claims abstract description 4
- 239000000203 mixture Substances 0.000 claims abstract description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 9
- 229960001866 silicon dioxide Drugs 0.000 claims description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 6
- 235000019441 ethanol Nutrition 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 5
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 4
- 238000004587 chromatography analysis Methods 0.000 claims description 3
- 239000003208 petroleum Substances 0.000 claims description 3
- 229910052786 argon Inorganic materials 0.000 claims description 2
- 239000007789 gas Substances 0.000 claims description 2
- 239000011261 inert gas Substances 0.000 claims description 2
- 239000000047 product Substances 0.000 claims description 2
- 238000000746 purification Methods 0.000 abstract description 6
- 238000012805 post-processing Methods 0.000 abstract description 3
- 238000002156 mixing Methods 0.000 abstract 1
- 239000003921 oil Substances 0.000 description 5
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 230000029142 excretion Effects 0.000 description 3
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- PKJBWOWQJHHAHG-UHFFFAOYSA-N 1-bromo-4-phenylbenzene Chemical group C1=CC(Br)=CC=C1C1=CC=CC=C1 PKJBWOWQJHHAHG-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 208000014644 Brain disease Diseases 0.000 description 1
- 208000032274 Encephalopathy Diseases 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 238000007341 Heck reaction Methods 0.000 description 1
- 206010020575 Hyperammonaemia Diseases 0.000 description 1
- JFLIEFSWGNOPJJ-JTQLQIEISA-N N(2)-phenylacetyl-L-glutamine Chemical compound NC(=O)CC[C@@H](C(O)=O)NC(=O)CC1=CC=CC=C1 JFLIEFSWGNOPJJ-JTQLQIEISA-N 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- IPBVNPXQWQGGJP-UHFFFAOYSA-N acetic acid phenyl ester Natural products CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229940049953 phenylacetate Drugs 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- -1 quinoline-8-yl Chemical group 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 229920002379 silicone rubber Polymers 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/41—Preparation of salts of carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/38—Nitrogen atoms
- C07D215/40—Nitrogen atoms attached in position 8
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a kind of preparation methods of phenylbutyrate sodium.The present invention is by under an inert atmosphere, being added to material and anhydrous 2,3-butanediol in reaction vessel and mixing；The associated materials include chlorination Allylpalladium (II) dimer, 2- (dicyclohexyl phosphono) -1- phenyl -1H- pyrroles, N- (eight aminoquinolines) butyl- 3- acrylamide, lithium acetate, bromobenzene, cyanoacetic acid and water；Reaction vessel is placed in 125~135 DEG C of oil baths and is vigorously stirred reaction 12 hours, reaction product is passed through into silica gel column purification, obtains the compound with homing device；Compound is added in the alcohol solvent containing sodium hydroxide, and heats the mixture to 130~140 DEG C of back flow reactions 12 hours, reaction product removes solvent, extraction through vacuum distillation, collects water layer, vacuum distillation removing water, obtains Buphenyl.The present invention has the characteristics that conversion zone selectivity and yield are high, reaction condition is mild, reaction and post-processing purification process are simple.
Description
Technical field
The invention belongs to technical field of organic chemistry more particularly to a kind of preparation methods of phenylbutyrate sodium.
Background technique
Phenylbutyrate sodium is pro-drug, can rapid metabolization at phenylacetate.It can generate benzene second in conjunction with glutamic acid and ammonia
Acyl glutamine is another approach of nitrogenouz wastes excretion by kidney excretion.Excessively high blood ammonia water can be made by taking phenylbutyrate sodium
Gentle blood aminoglutaric acid concentration decline, increases the excretion of nitrogenouz wastes in the form of forming phenylacetylglutamine.Suitable for all new
Raw youngster's azymia (being shown as in 28d after birth completely enzymoprivic), the Delayed onset azymia for having hyperammonemia encephalopathy family history
The patient of (part azymia is shown as after the first month of birth).
But in the synthetic method of existing phenylbutyrate sodium, generally existing synthesis step is more, conversion zone selectivity compared with
The problems such as difference, product yield is low, and reaction condition is not mild, reaction and complex post-processing purification process.
Summary of the invention
The primary purpose of the present invention is that providing a kind of preparation method of phenylbutyrate sodium, it is intended to overcome the deficiencies in the prior art
Place.
The invention is realized in this way a kind of preparation method of phenylbutyrate sodium, method includes the following steps:
(1) under an inert atmosphere, material and anhydrous 2,3-butanediol are added to instead by a mole volume ratio 0.1mmol:1mL
It answers in container and mixes；Wherein, it is 1:(1~3 that the associated materials, which include molar ratio): (0.01~0.1): (0.02~0.2): (1
~5): (1~3): N- (eight aminoquinolines) the butyl- 3- acrylamide of (1~100), bromobenzene, chlorination Allylpalladium (II) dimer,
2- (dicyclohexyl phosphono) -1- phenyl -1H- pyrroles, lithium acetate, cyanoacetic acid and water；
(2) reaction vessel is placed in 125~135 DEG C of oil baths and is vigorously stirred reaction 12 hours, reaction product is passed through into silicon
Rubber column gel column purifying, obtains the compound with homing device；
(3) compound is added in the alcohol solvent containing sodium hydroxide, and heat the mixture to 130~
140 DEG C back flow reaction 12 hours；Wherein, the compound, sodium hydroxide, ethyl alcohol molar ratio be 1:(1.5~4): (5~
50)；Reaction product is removed into solvent through vacuum distillation, water layer is collected in extraction, and vacuum distillation removes water, obtains phenylbutyrate sodium system
Agent.
Preferably, in step (1), inert gas used in the inert atmosphere is argon gas.
Preferably, in step (2), the silica gel column purification is to wash away chromatography silicon than upper ethyl acetate 1:20 with petroleum ether
Rubber column gel column.
Preferably, in step (3), the pressure of the vacuum distillation is within 100mbar, temperature is 80 DEG C or more；Institute
Extraction is stated to be extracted by the way that methylene chloride is added.
In order to overcome the shortcomings of the prior art and step, the invention discloses the invention discloses a kind of preparations of phenylbutyrate sodium
Method.In the present invention, by under an inert atmosphere, material and anhydrous 2,3-butanediol being pressed mole volume ratio 0.1mmol:1mL
It is added in reaction vessel and mixes；Wherein, the associated materials include chlorination Allylpalladium (II) dimer, 2- (dicyclohexyl
Phosphono) -1- phenyl -1H- pyrroles, N- (eight aminoquinolines) butyl- 3- acrylamide, lithium acetate, 4- bromo biphenyl, cyanoacetic acid and
Water；Reaction vessel is placed in 125~135 DEG C of oil baths and is vigorously stirred reaction 12 hours, reaction product is passed through into silica gel column purification,
Obtain compound 4- phenyl-N- (quinoline-8-yl) butyramide with homing device.
The compound can be used for synthesizing phenylbutyrate sodium, and the synthetic reaction process of phenylbutyrate sodium is as follows:
Compared with the prior art the shortcomings that and deficiency, the invention has the following advantages: the present invention passes through reduction HECK
Reaction, eight aminoquinolines of design control region and chemo-selective in reaction as the compound of homing device, effectively solve
The excessive problem of step in existing phenylbutyrate sodium synthesis process of having determined；Also, the present invention has conversion zone selectivity and yield
Feature high, reaction condition is mild, reaction and post-processing purification process are simple.
Specific embodiment
In order to make the objectives, technical solutions, and advantages of the present invention clearer, with reference to embodiments, to the present invention
It is further elaborated.It should be appreciated that the specific embodiments described herein are merely illustrative of the present invention, it is not used to
Limit the present invention.
Embodiment 1
(1) under an argon atmosphere, material and anhydrous 2,3-butanediol are added to by a mole volume ratio 0.1mmol:0.1mL
It is mixed in reaction vessel；Wherein, the associated materials include N- (the eight amino quinolines that molar ratio is 1:3:0.01:0.2:5:3:100
Quinoline) butyl- 3- acrylamide, bromobenzene, chlorination Allylpalladium (II) dimer, 2- (dicyclohexyl phosphono) -1- phenyl -1H- pyrroles,
Lithium acetate, cyanoacetic acid and water；
(2) reaction vessel is placed in 125 DEG C of oil baths and is vigorously stirred reaction 12 hours, reaction product is pure by silicagel column
Change (washing away chromatography silica gel column than upper ethyl acetate 1:20 with petroleum ether), obtains the compound with homing device, it is true through detecting
The fixed compound is 4- phenyl-N- (quinoline-8-yl) butyramide.
Embodiment 2
The present embodiment is substantially the same manner as Example 1, and difference is:
In step (1), N- (eight aminoquinolines) butyl- 3- acrylamide, bromobenzene, chlorination Allylpalladium (II) dimer, 2-
(dicyclohexyl phosphono) -1- phenyl -1H- pyrroles, lithium acetate, cyanoacetic acid and water molar ratio be 1:1:0.1:0.02:1:
1:1；
In step (2), oil bath temperature is 130 DEG C.
Embodiment 3
The present embodiment is substantially the same manner as Example 1, and difference is:
In step (1), N- (eight aminoquinolines) butyl- 3- acrylamide, bromobenzene, chlorination Allylpalladium (II) dimer, 2-
(dicyclohexyl phosphono) -1- phenyl -1H- pyrroles, lithium acetate, cyanoacetic acid and water molar ratio be 1:2:0.05:0.1:3:
2:50；
In step (2), oil bath temperature is 135 DEG C.
Embodiment 4
(1) by 4- phenyl-N- (quinoline-8-yl) butyramide being prepared in embodiment 2 to the second containing sodium hydroxide
In alcoholic solvent, and heat the mixture to 130~140 DEG C of back flow reactions 12 hours；Wherein, 4- phenyl-N- (quinoline-8-yl) fourth
Amide, sodium hydroxide, ethyl alcohol molar ratio be 1:4:50；
(2) by the back flow reaction product in step (1), by vacuum distillation, (pressure is within 100mbar, temperature is 80 DEG C
More than) remove solvent, be added methylene chloride extract 3 times, collect water layer, distillation under vacuum (pressure be 100mbar within, temperature
Be 80 DEG C or more) remove reaction product in reaction dissolvent (predominantly water), obtain Buphenyl 1.
Embodiment 5
The present embodiment is substantially the same manner as Example 1, obtains Buphenyl 2, difference is: in step
(1) in, 4- phenyl-N- (quinoline-8-yl) butyramide, sodium hydroxide, ethyl alcohol molar ratio be 1:1.5:5.
The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all in essence of the invention
Made any modifications, equivalent replacements, and improvements etc., should all be included in the protection scope of the present invention within mind and principle.
Claims (4)
1. a kind of preparation method of phenylbutyrate sodium, which is characterized in that method includes the following steps:
(1) under an inert atmosphere, material and anhydrous 2,3-butanediol reaction is added to by a mole volume ratio 0.1mmol:1mL to hold
It is mixed in device；Wherein, it is 1:(1~3 that the associated materials, which include molar ratio): (0.01~0.1): (0.02~0.2): (1~
5): (1~3): N- (eight aminoquinolines) the butyl- 3- acrylamide of (1~100), bromobenzene, chlorination Allylpalladium (II) dimer, 2-
(dicyclohexyl phosphono) -1- phenyl -1H- pyrroles, lithium acetate, cyanoacetic acid and water；
(2) reaction vessel is placed in 125~135 DEG C of oil baths and is vigorously stirred reaction 12 hours, reaction product is passed through into silicagel column
Purifying obtains the compound with homing device；
(3) compound is added in the alcohol solvent containing sodium hydroxide, and heats the mixture to 130~140 DEG C
Back flow reaction 12 hours；Wherein, the compound, sodium hydroxide, ethyl alcohol molar ratio be 1:(1.5~4): (5~50)；It will be anti-
Product is answered to remove solvent through vacuum distillation, water layer is collected in extraction, and vacuum distillation removes water, obtains Buphenyl.
2. the preparation method of phenylbutyrate sodium as described in claim 1, which is characterized in that in step (1), the inert atmosphere
Inert gas used is argon gas.
3. the preparation method of phenylbutyrate sodium as described in claim 1, which is characterized in that in step (2), the silicagel column is pure
It turns to and washes away chromatography silica gel column than upper ethyl acetate 1:20 with petroleum ether.
4. the preparation method of phenylbutyrate sodium as described in claim 1, which is characterized in that in step (3), the vacuum distillation
Pressure be within 100mbar, temperature is 80 DEG C or more；The extraction is to be extracted by the way that methylene chloride is added.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910681637.4A CN110317132B (en) | 2019-07-26 | 2019-07-26 | Preparation method of sodium phenylbutyrate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910681637.4A CN110317132B (en) | 2019-07-26 | 2019-07-26 | Preparation method of sodium phenylbutyrate |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110317132A true CN110317132A (en) | 2019-10-11 |
| CN110317132B CN110317132B (en) | 2021-09-10 |
Family
ID=68124634
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910681637.4A Active CN110317132B (en) | 2019-07-26 | 2019-07-26 | Preparation method of sodium phenylbutyrate |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110317132B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113121373A (en) * | 2021-04-16 | 2021-07-16 | 南京工业大学 | Method for synthesizing chlorambucil |
| CN115215798A (en) * | 2022-06-10 | 2022-10-21 | 恒升德康(南京)医药科技有限公司 | Aromatic cyaniding synthesis method of inert olefin |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1511133A (en) * | 2001-05-21 | 2004-07-07 | R������˹�� ˹̹��˹�� | Synthesis of 4-Phenylbutyric acid |
| CN1791606A (en) * | 2003-05-16 | 2006-06-21 | 德古萨股份公司 | Nitrogen-containing monodentate phosphines and their use in catalysis |
| CN108658857A (en) * | 2018-06-14 | 2018-10-16 | 南京工业大学 | A kind of method of synthesis of carboxylic acid derivative |
-
2019
- 2019-07-26 CN CN201910681637.4A patent/CN110317132B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1511133A (en) * | 2001-05-21 | 2004-07-07 | R������˹�� ˹̹��˹�� | Synthesis of 4-Phenylbutyric acid |
| CN1791606A (en) * | 2003-05-16 | 2006-06-21 | 德古萨股份公司 | Nitrogen-containing monodentate phosphines and their use in catalysis |
| CN108658857A (en) * | 2018-06-14 | 2018-10-16 | 南京工业大学 | A kind of method of synthesis of carboxylic acid derivative |
Non-Patent Citations (4)
| Title |
|---|
| CHENGDONG WANG ET AL.: "Palladium-Catalyzed Regiocontrollable Reductive Heck Reaction of Unactivated Aliphatic Alkenes", 《J. AM. CHEM. SOC.》 * |
| HONGGUI LV: "Nickel(0)-catalyzed linear-selective hydroarylation of unactivated alkenes and styrenes with aryl boronic acids", 《CHEM. SCI.》 * |
| JOSEPH DEROSA ET AL.: "Nickel-Catalyzed β,γ-Dicarbofunctionalization of Alkenyl Carbonyl Compounds via Conjunctive Cross-Coupling", 《J. AM. CHEM. SOC.》 * |
| YUN ZHANG ET AL.: "Three-component vicinal-diarylation of alkenes via direct transmetalation of arylboronic acids", 《CHEM. SCI.》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113121373A (en) * | 2021-04-16 | 2021-07-16 | 南京工业大学 | Method for synthesizing chlorambucil |
| CN115215798A (en) * | 2022-06-10 | 2022-10-21 | 恒升德康(南京)医药科技有限公司 | Aromatic cyaniding synthesis method of inert olefin |
| CN115215798B (en) * | 2022-06-10 | 2024-02-06 | 恒升德康(南京)医药科技有限公司 | Aromatic cyanation synthesis method of inert olefin |
Also Published As
| Publication number | Publication date |
|---|---|
| CN110317132B (en) | 2021-09-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Cavender et al. | Trifluoromethanesulfonyl azide. Its reaction with alkyl amines to form alkyl azides | |
| CN110317132A (en) | A kind of preparation method of phenylbutyrate sodium | |
| CN105085413B (en) | Tetrahydroquinazoline-2-schiff base compounds as well as synthesis method and application thereof | |
| Brown et al. | A convenient procedure for upgrading commercial (+)-and (-)-. alpha.-pinene to material of high optical purity | |
| CN109232178B (en) | Novel method for preparing high-purity hydroxytyrosol | |
| CN102822339A (en) | Method for precipitating anionic surfactant ions in presence of nucleic acids | |
| CN109704926A (en) | Anticancer activity molecular skeleton 1,4- enyne compounds and the preparation method and application thereof | |
| CN104418861B (en) | A kind of preparation method of Xi Gelieting midbody compound | |
| CN109096126B (en) | Deuterium labeled D9Synthesis method of clenbuterol hydrochloride | |
| CN104530090B (en) | A kind of preparation method of pyridine derivate | |
| CN107827791A (en) | A kind of synthetic method of the Thiamphenicol of cold labeling | |
| CN105175276A (en) | Synthetic method for optically pure(R)-3-carbamyl methyl-5-methyl caproic acid | |
| CN109851615A (en) | The method for purifying amyl ethyl quin ether | |
| CN110352187A (en) | Acrylamide method | |
| CN110845349B (en) | Purification method of Sacubitril valsartan sodium intermediate | |
| CN114213306A (en) | Preparation method of brivaracetam acid impurity | |
| CN108530359A (en) | A kind of preparation method of Ivabradine impurity | |
| CN103588825A (en) | Method for protecting D-glucosamine derivative by using benzaldehyde dimethyl acetal | |
| CN107325122B (en) | Novel intermediate for preparing prostaglandins and preparation method thereof | |
| WO2008152888A1 (en) | Method of purifying microorganisms and method of detecting microorganisms | |
| US8263786B2 (en) | Methods for producing cyclic phenol sulfides | |
| CN115650824B (en) | Chiral diol and preparation method thereof, prepared catalyst and preparation method and application thereof | |
| CN105254496A (en) | Methyl bromoacetate synthesis method | |
| CN107513046A (en) | Synthesis method of Coxstat | |
| CN105622434B (en) | The preparation method of 1 (2,5 Dimethoxyphenyl) 2 ethylaminoethanols |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |