CN106588698A - Preparation method of N-Boc biphenyl alaninal - Google Patents
Preparation method of N-Boc biphenyl alaninal Download PDFInfo
- Publication number
- CN106588698A CN106588698A CN201611015731.9A CN201611015731A CN106588698A CN 106588698 A CN106588698 A CN 106588698A CN 201611015731 A CN201611015731 A CN 201611015731A CN 106588698 A CN106588698 A CN 106588698A
- Authority
- CN
- China
- Prior art keywords
- oxidation reaction
- boc
- preparation
- biphenyl
- iodosobenzoic acids
- 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C269/00—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C269/06—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups by reactions not involving the formation of carbamate groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of N-Boc-biphenyl alaninal, and the preparation method comprises the following steps: the N-Boc-biphenyl alaninal can be obtained by oxidation reaction of N-Boc-biphenyl alaninol and 2-iodoxybenzoic acid in an organic solvent. The method has the advantages of simple operation, high yield, high purity, low cost and little pollution, and is suitable for industrial production.
Description
Technical field
The present invention relates to a kind of preparation method of the ammonium aldehyde of N-Boc biphenyl third, belongs to field of medicine and chemical technology.
Background technology
The new drug Entresto of the treatment angiocardiopathy that Novartis Co., Ltd releases recently, for treating II-IV grade of heart of NYHA
Decline patient, in many ways cardioactive neuroendocrine system.Entresto is the anti-hypertension for losing patent protection
Medicine Valsartan and a kind of combination drug of novel antihypertensive medicament Sacubitril, for the treatment of heart failure.
For the synthesis of newtype drug Sacubitril enkephalinase inhibitors, though document has the report of several different routes
Road, but the conversion that N-Boc biphenyl Propanolamines are converted into the ammonium aldehyde of N-Boc biphenyl third is directed to mostly.Relevant this oxidizing process,
Nine divisions of China in remote antiquity medicine company and Novartis Co., Ltd are only seen at present reports the technique using TEMPO catalysis oxidations in WO2014032627.The work
The advantage of skill is that raw material is relatively inexpensive, but cumbersome, and solvent load is big, and system is huge, and the yield of products therefrom is typically 70
～75%.
Therefore, this area need badly a kind of simple to operate, high income, purity height, low cost, pollution less, be adapted to industrial metaplasia
The preparation method of the ammonium aldehyde of N-Boc- biphenyl third of product.
The content of the invention
Problem to be solved by this invention be the existing ammonium aldehyde of N-Boc- biphenyl third preparation method is cumbersome, yield is low
Etc. defect, thus, the invention provides a kind of preparation method of the ammonium aldehyde of N-Boc- biphenyl third.The method is simple to operate, high income,
Purity height, low cost, pollution less, be adapted to industrialized production.
The invention provides a kind of preparation method of the ammonium aldehyde of N-Boc- biphenyl third, it comprises the steps：In organic solvent
In, N-Boc- biphenyl Propanolamine and 2- iodosobenzoic acids (IBX) are carried out into oxidation reaction, obtain the ammonium aldehyde of N-Boc- biphenyl third i.e.
Can；
Wherein, " * " in described N-Boc- biphenyl Propanolamine and the described ammonium aldehyde of N-Boc- biphenyl third represents mark
Carbon atom is asymmetric carbon atom, and its configuration it is identical (therefore, described N-Boc- biphenyl Propanolamine and described N-Boc- biphenyl
Third ammonium aldehyde is simultaneously R configurations, S configurations or, the mixture of R configurations and S configurations；Namely there is no configuration reversal in the reaction).
In described oxidation reaction, described organic solvent can be the conventional organic solvent of such reaction of this area, this
Invent one or more in particularly preferred nitrile solvents, aromatic hydrocarbon solvent and ether solvent, further preferred ether solvent.
Described ether solvent can be the conventional ether solvent of such reaction of this area, 1,2- dimethoxy-ethanes specifically preferred according to the invention
(DME).Described aromatic hydrocarbon solvent can be the conventional aromatic hydrocarbon solvent of such reaction of this area, first specifically preferred according to the invention
Benzene.Described nitrile solvents can be the conventional nitrile solvents of such reaction of this area, acetonitrile specifically preferred according to the invention.
In described oxidation reaction, the volume mass ratio of described organic solvent and described N-Boc- biphenyl Propanolamines
Can be the conventional volume mass ratio of such reaction of this area, preferably 3～12mL/g is more preferably 4～8mL/g, most preferably
For 5～6mL/g.
In described oxidation reaction, described 2- iodosobenzoic acids and described N-Boc- biphenyl Propanolamines mole
Than being the conventional mol ratio of such reaction of this area, preferably 1.0～2.0, more preferably for 1.1～1.6 (such as 1.3～
1.4)。
In described oxidation reaction, the temperature of described oxidation reaction can be the conventional temperature of such reaction of this area,
Preferably 30～120 DEG C (and such as 110 DEG C), are more preferably 50～90 DEG C, are most preferably 75～85 DEG C.
In described oxidation reaction, described oxidation reaction such reaction conventional detection mode can be carried out using this area
Monitoring, such as thin-layer chromatography (TLC).When reaction end monitoring is carried out with TLC, typically no longer reacted with N-Boc- biphenyl Propanolamines
As the terminal of reaction.The time of described oxidation reaction can be (such as 0.5～2 hour, and such as 1 is little 0.5～3 hour
When).
Described oxidation reaction can also include the conventional post processing of such reaction of this area.It is preferred that described oxidation is anti-
Following post-processing steps should also be included：Cooling (being for example down to room temperature), filters, with above-mentioned organic solvent washing filter cake (i.e. 2-
Iodosobenzoic acid crude product), filtrate concentration (partially completely removes reaction dissolvent, above-mentioned organic solvent), recrystallization
(recrystallization solvent can be ethyl acetate/normal heptane), obtains the described ammonium aldehyde of N-Boc- biphenyl third.
It is preferred that the post-processing step of described oxidation reaction also comprises the steps, in processing in the above-mentioned latter
The filter cake (i.e. 2- iodosobenzoic acids crude product) that obtains is reoxidized for 2- iodosobenzoic acids, so as to realize recycling,
And work well：In water, described filter cake (i.e. 2- iodosobenzoic acids crude product) and oxidant are carried out into oxidation reaction, obtained
To 2- iodosobenzoic acids；
In the preparation method of described 2- iodosobenzoic acids, described oxidant can be such reaction routine of this area
Oxidant (such as potassium permanganate or potassium hydrogen persulfate), preferably potassium hydrogen persulfate.
In the preparation method of described 2- iodosobenzoic acids, described oxidant and described filter cake (i.e. 2- idous
Acyl group benzoic acid crude product) mol ratio can be the conventional mol ratio of such reaction of this area, preferably 2.0～3.6, more preferably
For 2.7～3.0.When the mole of described filter cake is calculated, it is assumed that described filter cake is 2- iodosobenzoic acid sterlings.
In the preparation method of described 2- iodosobenzoic acids, the temperature of described oxidation reaction can for this area such
The conventional temperature of reaction, preferably 30～100 DEG C, be more preferably 50～90 DEG C, is most preferably 65～75 DEG C.
In the preparation method of described 2- iodosobenzoic acids, described oxidation reaction can be using such reaction of this area
Conventional detection mode is monitored, such as thin-layer chromatography (TLC).When reaction end monitoring is carried out with TLC, typically with 2- iodosos
Yl benzoic acid residual is less than 2% as the terminal of reaction.
Without prejudice to the field on the basis of common sense, above-mentioned each optimum condition, can be combined, and obtain final product the present invention each preferably
Example.
Agents useful for same of the present invention and raw material are commercially available.
The present invention positive effect be：The method is simple to operate, high income, purity height, low cost, pollution less,
Suitable industrialized production
Specific embodiment
The present invention is further illustrated below by the mode of embodiment, but does not therefore limit the present invention to described reality
Among applying a scope.The experimental technique of unreceipted actual conditions in the following example, conventionally and condition, or according to business
Product specification is selected.
The measuring method of embodiment moderate purity is as follows：HPLC, chromatographic column：Gemini C18,250 × 4.6mmID, 5 μm, stream
Speed：1.0mL/min, column temperature：30℃.Mobile phase A (20mM KH2PO4The aqueous solution, adds 6mol/L KOH to adjust pH=10), stream
Dynamic phase B (MeOH).Gradient:0min (70%A)；20min (30%A)；40min (30%A).Acquisition time：40 minutes.
Retention time：
(R)-N-Boc-3- (1,1 '-biphenyl -4- bases) -2- aminopropanols：30.3min
(R)-N-Boc-3- (1,1 '-biphenyl -4- bases) -2- amido propionic aldehyde：32.0min
2- iodosobenzoic acids：3.4min
2- iodosobenzoic acids：4.2min
Embodiment 1 (R)-N-Boc-3- (1,1 '-biphenyl -4- bases) -2- amido propionic aldehyde
In the round-bottomed flask of 1L, 105g (R)-N-Boc-3- (1,1 '-biphenyl -4- bases) -2- aminopropanols are dissolved in
In 600mL DME, under stirring, 117g IBX are added.After adding, reaction system is heated to into 75-85 DEG C, is reacted 1 hour
Left and right monitors to raw material and disappears, and reaction system is cooled down to into room temperature.Filter, filter cake 50mL DME drip washing, after filter cake is collected
As 2- iodosobenzoic acids, for follow-up recovery, after filtrate reduced in volume, with ethyl acetate/normal heptane crystallization, drying
After obtain white solid 101g, as target product.Yield 96.6%, purity>99%.
1H-NMR(400MHz,CDCl3):δ=9.69 (s, 1H), 7.59 (t, 4H), 7.46 (t, 2H), 7.38 (t, 1H),
7.28(d,2H),5.13(d,1H),4.48(q,1H),3.18(d,2H),1.47(s,9H)。
Embodiment 2 prepares IBX with the 2- iodosobenzoic acids for reclaiming
In the round-bottomed flask of 1L, the 2- iodosobenzoic acids reclaimed in 40g above-described embodiments 1 are added, add configuration
(145g potassium hydrogen persulfates are dissolved in 500mL water good hydrogen persulfate aqueous solutions of potassium, and the active constituent content of potassium hydrogen persulfate is
42.8%).After adding, reaction system is heated to into 65-75 DEG C, is reacted 3 hours or so, monitored to 2- idous acyl group benzene first
Acid residual is less than 2%.Reaction system is cooled down to into 0-5 DEG C, is stirred 2 hours.Filter, filter cake is washed with water repeatedly, after drying
Obtain white solid 38.6g, as IBX.The rate of recovery 85.4%, purity>98%.
(IBX is with the 2- iodosos for reclaiming to embodiment 3 (R)-N-Boc-3- (1,1 '-biphenyl -4- bases) -2- amido propionic aldehyde
Yl benzoic acid prepares gained)
In the round-bottomed flask of 250mL, 26g (R)-N-Boc-3- (1,1 '-biphenyl -4- bases) -2- aminopropanols are dissolved in
In 160mL DME, under stirring, the IBX that preparation is reclaimed in 29g embodiments 2 is added.After adding, reaction system is heated to
75-85 DEG C, reaction is monitored to raw material and disappeared for 1 hour or so, and reaction system is cooled down to into room temperature.Filter, filter cake 15mL
DME drip washing, as 2- iodosobenzoic acids after filter cake collection, can be repeated for follow-up recovery.After filtrate reduced in volume, use
Ethyl acetate/normal heptane crystallization, obtains white solid 25g, as target product after drying.Yield 96.4%, purity>99%.
Embodiment 4 (S)-N-Boc-3- (1,1 '-biphenyl -4- bases) -2- amido propionic aldehyde
In the round-bottomed flask of 1L, 105g (S)-N-Boc-3- (1,1 '-biphenyl -4- bases) -2- aminopropanols are dissolved in
In 300mL acetonitriles, under stirring, 90g IBX are added.After adding, reaction system is heated to into 50-55 DEG C, reacts 2 hours left sides
Right monitoring to raw material disappears, and reaction system is cooled down to into room temperature.Filter, filter cake 50mL acetonitrile drip washing, filter cake is made after collecting
For 2- iodosobenzoic acids, for follow-up recovery, after filtrate reduced in volume, crystallized with ethyl acetate/normal heptane, after drying
Obtain white solid 92g, as target product.Yield 88%, purity>98%.
Embodiment 5 (R)-N-Boc-3- (1,1 '-biphenyl -4- bases) -2- amido propionic aldehyde
In the round-bottomed flask of 1L, 105g (R)-N-Boc-3- (1,1 '-biphenyl -4- bases) -2- aminopropanols are dissolved in
In 800mL toluene, under stirring, 144g IBX are added.After adding, reaction system is heated to into 110 DEG C of backflows, reaction 1 is little
When or so monitor to raw material disappear, reaction system is cooled down to into room temperature.Filter, filter cake 50mL toluene drip washing, filter cake is collected
Afterwards as 2- iodosobenzoic acids, for follow-up recovery, after filtrate reduced in volume, with ethyl acetate/normal heptane crystallization, dry
White solid 89g, as target product are obtained after dry.Yield 85%, purity>99%.
Embodiment 6 (R)-N-Boc-3- (1,1 '-biphenyl -4- bases) -2- amido propionic aldehyde
In the round-bottomed flask of 1L, 105g (R)-N-Boc-3- (1,1 '-biphenyl -4- bases) -2- aminopropanols are dissolved in
In 400mL DME, under stirring, 100g IBX are added.After adding, reaction system is heated to into 30～35 DEG C, is reacted 3 hours
Left and right monitors to raw material and disappears, and reaction system is cooled down to into room temperature.Filter, filter cake 50mL DME drip washing, after filter cake is collected
As 2- iodosobenzoic acids, for follow-up recovery, after filtrate reduced in volume, with ethyl acetate/normal heptane crystallization, drying
After obtain white solid 97g, as target product.Yield 93%, purity>99%.
Embodiment 7 (R)-N-Boc-3- (1,1 '-biphenyl -4- bases) -2- amido propionic aldehyde
In the round-bottomed flask of 1L, 105g (R)-N-Boc-3- (1,1 '-biphenyl -4- bases) -2- aminopropanols are dissolved in
In 1200mL toluene, under stirring, 180g IBX are added.After adding, reaction system is heated to into 90-95 DEG C, is reacted 1 hour
Left and right monitors to raw material and disappears, and reaction system is cooled down to into room temperature.Filter, filter cake 50mL toluene drip washing, after filter cake is collected
As 2- iodosobenzoic acids, for follow-up recovery, after filtrate reduced in volume, with ethyl acetate/normal heptane crystallization, drying
After obtain white solid 90g, as target product.Yield 86%, purity>98%.
Claims (10)
1. a kind of preparation method of the ammonium aldehyde of N-Boc- biphenyl third, it comprises the steps：In organic solvent, by N-Boc- biphenyl
Propanolamine and 2- iodosobenzoic acids carry out oxidation reaction, obtain the ammonium aldehyde of N-Boc- biphenyl third；
Wherein, " * " in described N-Boc- biphenyl Propanolamine and the described ammonium aldehyde of N-Boc- biphenyl third represents that the carbon of mark is former
Son is asymmetric carbon atom, and its configuration is identical.
2. preparation method as claimed in claim 1, it is characterised in that described N-Boc- biphenyl Propanolamine and described N-
The ammonium aldehyde of Boc- biphenyl third is simultaneously R configurations, S configurations or, the mixture of R configurations and S configurations；
And/or, in described oxidation reaction, described organic solvent is nitrile solvents, aromatic hydrocarbon solvent and ether solvent
In one or more；
And/or, in described oxidation reaction, the volume mass of described organic solvent and described N-Boc- biphenyl Propanolamines
Than for 3～12mL/g；
And/or, in described oxidation reaction, described 2- iodosobenzoic acids rub with described N-Boc- biphenyl Propanolamines
You are than being 1.0～2.0；
And/or, the temperature of described oxidation reaction is 30～120 DEG C；
And/or, described oxidation reaction no longer reacts the terminal as reaction using N-Boc- biphenyl Propanolamine.
3. preparation method as claimed in claim 2, it is characterised in that in described oxidation reaction, described nitrile solvents
For acetonitrile；
And/or, in described oxidation reaction, described aromatic hydrocarbon solvent is toluene；
And/or, in described oxidation reaction, described ether solvent is 1,2- dimethoxy-ethanes；
And/or, in described oxidation reaction, the volume mass of described organic solvent and described N-Boc- biphenyl Propanolamines
Than for 4～8mL/g；
And/or, in described oxidation reaction, described 2- iodosobenzoic acids rub with described N-Boc- biphenyl Propanolamines
You are than being 1.1～1.6；
And/or, the temperature of described oxidation reaction is 50～90 DEG C.
4. preparation method as claimed in claim 3, it is characterised in that in described oxidation reaction, described organic solvent
It is 5～6mL/g with the volume mass ratio of described N-Boc- biphenyl Propanolamines；
And/or, in described oxidation reaction, described 2- iodosobenzoic acids rub with described N-Boc- biphenyl Propanolamines
You are than being 1.3～1.4；
And/or, the temperature of described oxidation reaction is 75～85 DEG C.
5. preparation method as claimed in claim 1, it is characterised in that described oxidation reaction also includes following post processing steps
Suddenly：Cooling, filters, and with described organic solvent washing filter cake, filtrate concentration, recrystallization obtains described N-Boc- biphenyl third
Ammonium aldehyde.
6. preparation method as claimed in claim 5, it is characterised in that described cooling is to be down to room temperature；
And/or, the solvent that described recrystallization is used is ethyl acetate and normal heptane.
7. preparation method as claimed in claim 5, it is characterised in that the post-processing step of described oxidation reaction, also includes
Following step：In water, described filter cake and oxidant are carried out into oxidation reaction, obtain 2- iodosobenzoic acids.
8. preparation method as claimed in claim 7, it is characterised in that in the preparation method of described 2- iodosobenzoic acids
In, described oxidant is potassium permanganate or potassium hydrogen persulfate；
And/or, in the preparation method of described 2- iodosobenzoic acids, the mol ratio of described oxidant and described filter cake
For 2.0～3.6；
And/or, in the preparation method of described 2- iodosobenzoic acids, the temperature of described oxidation reaction is 30～100 DEG C；
And/or, in the preparation method of described 2- iodosobenzoic acids, described oxidation reaction is with 2- iodosobenzoic acids
Residual is less than 2% as the terminal of reaction.
9. preparation method as claimed in claim 8, it is characterised in that in the preparation method of described 2- iodosobenzoic acids
In, described oxidant is potassium hydrogen persulfate；
And/or, in the preparation method of described 2- iodosobenzoic acids, the mol ratio of described oxidant and described filter cake
For 2.7～3.0；
And/or, in the preparation method of described 2- iodosobenzoic acids, the temperature of described oxidation reaction is 50～90 DEG C.
10. preparation method as claimed in claim 9, it is characterised in that in the preparation method of described 2- iodosobenzoic acids
In, the temperature of described oxidation reaction is 65～75 DEG C.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611015731.9A CN106588698B (en) | 2016-11-18 | 2016-11-18 | A kind of preparation method of the third ammonium aldehyde of N-Boc biphenyl |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611015731.9A CN106588698B (en) | 2016-11-18 | 2016-11-18 | A kind of preparation method of the third ammonium aldehyde of N-Boc biphenyl |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106588698A true CN106588698A (en) | 2017-04-26 |
| CN106588698B CN106588698B (en) | 2019-01-22 |
Family
ID=58592280
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201611015731.9A Active CN106588698B (en) | 2016-11-18 | 2016-11-18 | A kind of preparation method of the third ammonium aldehyde of N-Boc biphenyl |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106588698B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109293628A (en) * | 2018-09-29 | 2019-02-01 | 浙江国邦药业有限公司 | A method of preparing 2- iodosobenzoic acid |
| CN110128298A (en) * | 2019-06-13 | 2019-08-16 | 南京一心和医药科技有限公司 | The synthetic method of one seed sand library Ba Qu intermediate |
Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996026729A1 (en) * | 1995-03-02 | 1996-09-06 | Ciba-Geigy Ag | Phosphono substituted tetrazole derivatives as ece inhibitors |
| CN101070315A (en) * | 2007-05-11 | 2007-11-14 | 江苏工业学院 | Method for preparing omeprazole |
| CN101508631A (en) * | 2009-03-31 | 2009-08-19 | 贵州大学 | Method for oxidizing ethanol into corresponding aldehyde in catalyst action |
| US20120129779A1 (en) * | 2007-05-10 | 2012-05-24 | R&D-Biopharmaceuticals Gmbh | Tubulysine derivatives |
| CN102924499A (en) * | 2012-10-22 | 2013-02-13 | 四川大学 | Synthesis of L-3, 4, 5-trioxo-phenylalanine/aldehyde compounds |
| CN102964267A (en) * | 2011-09-01 | 2013-03-13 | 中山大学 | Cyclohexene compound having influenza virus neuraminidase inhibition activity, preparation method and application |
| CN103242146A (en) * | 2013-05-23 | 2013-08-14 | 天宁香料（江苏）有限公司 | Preparation method of cis-3-hexenal |
| CN105026361A (en) * | 2012-08-31 | 2015-11-04 | 浙江九洲药业股份有限公司 | New process |
| CN105168205A (en) * | 2015-08-18 | 2015-12-23 | 泰力特医药（湖北）有限公司 | Preparation method for dual inhibitor LCZ696 of angiotensin II receptor and neprilysin |
| CN106045902A (en) * | 2016-06-30 | 2016-10-26 | 苏州健雄职业技术学院 | Preparation method of 3-bromo-6-methyl-2-pyridylaldehyde |
-
2016
- 2016-11-18 CN CN201611015731.9A patent/CN106588698B/en active Active
Patent Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996026729A1 (en) * | 1995-03-02 | 1996-09-06 | Ciba-Geigy Ag | Phosphono substituted tetrazole derivatives as ece inhibitors |
| US20120129779A1 (en) * | 2007-05-10 | 2012-05-24 | R&D-Biopharmaceuticals Gmbh | Tubulysine derivatives |
| CN101070315A (en) * | 2007-05-11 | 2007-11-14 | 江苏工业学院 | Method for preparing omeprazole |
| CN101508631A (en) * | 2009-03-31 | 2009-08-19 | 贵州大学 | Method for oxidizing ethanol into corresponding aldehyde in catalyst action |
| CN102964267A (en) * | 2011-09-01 | 2013-03-13 | 中山大学 | Cyclohexene compound having influenza virus neuraminidase inhibition activity, preparation method and application |
| CN105026361A (en) * | 2012-08-31 | 2015-11-04 | 浙江九洲药业股份有限公司 | New process |
| CN102924499A (en) * | 2012-10-22 | 2013-02-13 | 四川大学 | Synthesis of L-3, 4, 5-trioxo-phenylalanine/aldehyde compounds |
| CN103242146A (en) * | 2013-05-23 | 2013-08-14 | 天宁香料（江苏）有限公司 | Preparation method of cis-3-hexenal |
| CN105168205A (en) * | 2015-08-18 | 2015-12-23 | 泰力特医药（湖北）有限公司 | Preparation method for dual inhibitor LCZ696 of angiotensin II receptor and neprilysin |
| CN106045902A (en) * | 2016-06-30 | 2016-10-26 | 苏州健雄职业技术学院 | Preparation method of 3-bromo-6-methyl-2-pyridylaldehyde |
Non-Patent Citations (2)
| Title |
|---|
| 胡跃飞等主编: "《现代有机反应》", 31 December 2008, 化学工业出版社 * |
| 覃开云等: "2- 碘酰基苯甲酸(2-Iodoxybenzoic acid, IBX)在有机合成中的应用", 《有机化学》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109293628A (en) * | 2018-09-29 | 2019-02-01 | 浙江国邦药业有限公司 | A method of preparing 2- iodosobenzoic acid |
| CN110128298A (en) * | 2019-06-13 | 2019-08-16 | 南京一心和医药科技有限公司 | The synthetic method of one seed sand library Ba Qu intermediate |
| CN110128298B (en) * | 2019-06-13 | 2021-08-03 | 南京一心和医药科技有限公司 | Synthetic method of Sacubitril intermediate |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106588698B (en) | 2019-01-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106588698B (en) | A kind of preparation method of the third ammonium aldehyde of N-Boc biphenyl | |
| Srivastava et al. | Direct sulfonylation of Baylis–Hillman alcohols and diarylmethanols with TosMIC in ionic liquid-[Hmim] HSO4: an unexpected reaction | |
| Wei et al. | Asymmetric synthesis of β-monosubstituted and β, β-disubstituted N-(p-toluenesulfinyl)-α-(aminoalkyl) acrylates via anionic additions of (α-carbalkoxyvinyl) cuprates to thiooxime S-oxides | |
| US3996246A (en) | Resolution of racemic pantolactone | |
| WO2008102375A2 (en) | A process for preparation of highly pure isotretinoin | |
| CN115353457B (en) | Asymmetric carbonate and preparation method thereof | |
| CN114773185B (en) | Method for synthesizing benzoyl fluoride compound by utilizing sodium trifluoromethanesulphinate | |
| DE10111262A1 (en) | Process for the preparation of vinyl aryl and heteroarylacetic acids and their derivatives | |
| CN112661667B (en) | Preparation method of trifluoroacetamidine | |
| CN113861034A (en) | Preparation method of 2-fluoro-3-nitrobenzoic acid | |
| CN114293210A (en) | Method for continuously electrosynthesis of benzopyran-4-ketone by using micro-reaction device | |
| CN110713442A (en) | Preparation method of o-nitrobenzaldehyde | |
| CN106748605B (en) | Method for synthesizing o-dicarbonyl aryl formate series compounds based on TBAB and Oxone methods | |
| CN112441961B (en) | Synthetic method of 3-pyrroline-2-ketone compound | |
| CN110128303B (en) | Method for synthesizing musk extract (2R,5R) -Musclide-A1 | |
| CN108147954B (en) | Preparation method of calcipotriol intermediate | |
| CN109369357B (en) | Method for preparing symmetrical diaryl ketone by catalytic oxidation carbonylation | |
| RU2612956C1 (en) | Method for producing 1-adamantyl acetaldehyde | |
| CN114644554A (en) | Preparation method of (S) -flurbiprofen and intermediate thereof | |
| CN106674011B (en) | A method of indenone derivative is synthesized by dimethyl sulfoxide | |
| CN110627647A (en) | High diastereoselectivity 2- (hydroxy (phenyl) methyl) cyclohexanone derivative and preparation method thereof | |
| CN105198796B (en) | The method of one kind synthesis carboxylic acid of S 1 [(S) 2 (3,4,5 2,4,5-trimethoxyphenyl) bytyry] piperidines 2 | |
| CN116023241A (en) | Phenanthrene ketone compound and preparation method thereof | |
| CN118619904A (en) | Alpha-methylene-gamma-butyrolactone derivative of condensed cyclohexene and synthetic method thereof | |
| CN118619819A (en) | Synthesis method of aromatic aldehyde |
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 |