CN103408399B - A kind of synthetic method with optically active alcohol - Google Patents
A kind of synthetic method with optically active alcohol Download PDFInfo
- Publication number
- CN103408399B CN103408399B CN201310364510.2A CN201310364510A CN103408399B CN 103408399 B CN103408399 B CN 103408399B CN 201310364510 A CN201310364510 A CN 201310364510A CN 103408399 B CN103408399 B CN 103408399B
- Authority
- CN
- China
- Prior art keywords
- formula
- compound
- solution
- optically active
- active alcohol
- 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.)
- Active
Links
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 title claims abstract description 12
- 238000010189 synthetic method Methods 0.000 title claims abstract description 10
- 150000001875 compounds Chemical class 0.000 claims abstract description 34
- 238000006243 chemical reaction Methods 0.000 claims abstract description 14
- 238000000034 method Methods 0.000 claims abstract description 11
- 230000002829 reductive effect Effects 0.000 claims abstract description 11
- 239000002904 solvent Substances 0.000 claims abstract description 11
- 239000002994 raw material Substances 0.000 claims abstract description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 45
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 27
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 15
- 238000003756 stirring Methods 0.000 claims description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 14
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 claims description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 12
- 238000005406 washing Methods 0.000 claims description 12
- 239000010410 layer Substances 0.000 claims description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- RTLMATDNIKWIIO-UHFFFAOYSA-N 2-n,2-n,6-n,6-n-tetrakis(2-chloroethyl)-4,8-di(piperidin-1-yl)pyrimido[5,4-d]pyrimidine-2,6-diamine Chemical compound C=12N=C(N(CCCl)CCCl)N=C(N3CCCCC3)C2=NC(N(CCCl)CCCl)=NC=1N1CCCCC1 RTLMATDNIKWIIO-UHFFFAOYSA-N 0.000 claims description 7
- 229910000085 borane Inorganic materials 0.000 claims description 7
- 239000012044 organic layer Substances 0.000 claims description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 6
- 239000007788 liquid Substances 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- RQXXCWHCUOJQGR-UHFFFAOYSA-N 1,1-dichlorohexane Chemical compound CCCCCC(Cl)Cl RQXXCWHCUOJQGR-UHFFFAOYSA-N 0.000 claims description 5
- 238000001291 vacuum drying Methods 0.000 claims description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 238000000605 extraction Methods 0.000 claims description 3
- 239000000463 material Substances 0.000 claims description 3
- 239000012074 organic phase Substances 0.000 claims description 3
- 229920006395 saturated elastomer Polymers 0.000 claims description 3
- 239000011780 sodium chloride Substances 0.000 claims description 3
- 235000002639 sodium chloride Nutrition 0.000 claims description 3
- 239000002035 hexane extract Substances 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 abstract description 6
- 239000003795 chemical substances by application Substances 0.000 abstract description 2
- 230000007423 decrease Effects 0.000 abstract description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 239000000126 substance Substances 0.000 abstract description 2
- 238000006722 reduction reaction Methods 0.000 description 9
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical group CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 2
- IBHOPHUUVQOHCC-UHFFFAOYSA-N B.c1cocn1 Chemical compound B.c1cocn1 IBHOPHUUVQOHCC-UHFFFAOYSA-N 0.000 description 1
- HVVNJUAVDAZWCB-YFKPBYRVSA-N [(2s)-pyrrolidin-2-yl]methanol Chemical compound OC[C@@H]1CCCN1 HVVNJUAVDAZWCB-YFKPBYRVSA-N 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention relates to chemical field, particularly the preparation field of compound, more specifically relate to a kind of synthetic method with optically active alcohol.The object of the invention is to find a kind of simple to operate, raw materials cost is low, purifying process is simple, has the synthetic method of optically active alcohol shown in the formula I that productive rate is high.The reduction of formula II compound is prepared type I compound by (S)-CBS-Me or (+)-DIP-Cl by the present invention, only use reductive agent, and corresponding solvent system, without the need to increasing other catalyzer, decrease raw material input cost, and reaction conditions is required loose, without the need to the severe condition such as high temperature, high pressure, be suitable for suitability for industrialized production.
Description
Technical field
The present invention relates to chemical field, particularly the preparation field of compound, more specifically relate to a kind of synthetic method with optically active alcohol.
Background technology
Type I compound
be a kind of important intermediate of receptor antagonist pharmaceuticals, the complex process degree of its synthesis, and the price of synthesis material, directly affect final cost of drugs.
In order to reduce medicine synthesising process difficulty, medicament-saving synthesis cost, we conduct extensive research the synthesis of type I compound, and find that conventional to go back the reduction effect of original reagent to type I compound poor, the yield of reduction after product is lower.And utilize general reduction reaction operating process, not only manipulation flow process is complicated, and expensive starting materials, is not suitable for industrialized mass.
Summary of the invention
The object of the invention is to find a kind of simple to operate, raw materials cost is low, purifying process is simple, has the synthetic method of optically active alcohol shown in the formula I that productive rate is high.
Concrete technical scheme is:
There is a synthetic method for optically active alcohol, described in there is optically active alcohol for compound shown in formula I,
(formula I),
Described type I compound is formed through reduction by formula II,
(formula II),
Its concrete reactions steps is as follows:
Add in enough solvents by compound shown in formula II, described solvent is any one in methylene dichloride, tetrahydrofuran (THF), ether, isopropyl ether, toluene;
Under nitrogen protection, abundant stirring and dissolving; Mixing solutions is cooled to-11 DEG C, adds the S-CBS-Me toluene solution of 1mol/L;
Drip the borane dimethylsulf iotade of 10mol/L, dropwise with the speed of 2.5 ~ 3ml/ min, in dropping process, keep system temperature lower than-8 DEG C;
Keep reaction system at-5 ~ 0 DEG C, utilize TLC to follow the tracks of, to raw material completely dissolve, drip successively methyl alcohol, 6% hydrogen peroxide and sulfuric acid, hierarchy of control temperature is lower than 0 DEG C; Stirring at room temperature 30min is risen to after dripping off;
Leave standstill, after solution layering, collect water layer and organic layer respectively;
Water layer dichloro hexane extracts, and by dichloro hexane extraction liquid and original machine also laminated;
Organic layer is used saturated aqueous common salt, water washing successively, then selects anhydrous sodium sulfate drying, concentrating under reduced pressure obtains oily matter;
Oily matter vacuum-drying at 20 DEG C, obtains type I compound;
The mol ratio of described formula II compound and borane dimethylsulf iotade is 1:1.1 ~ 1.5; The amount ratio of described formula II compound and S-CBS-Me is the S-CBS-Me solution that 1mol formula II compound adds 5% ~ 15%.
Wherein S-CBS-Me refers to the compound with following structure:
。
Described S-CBS-Me directly needs buying according to purity, or according to the preparation method's preparation in existing open source literature.
Further, we also disclosed the possibility of another reaction, reactions steps is as follows:
Add in enough solvents by compound shown in formula II, described solvent is any one in methylene dichloride, tetrahydrofuran (THF), ether, isopropyl ether, toluene;
Under nitrogen protection, abundant stirring and dissolving;
Under the temperature condition of 0 ~ 50 DEG C, drip (+) DIP-Cl, drop rate is 3.5 ~ 4.5g/min;
Keep reaction system at ambient temperature, utilize TLC to follow the tracks of, to raw material completely dissolve;
Evaporated under reduced pressure solution, adds methylene dichloride and dissolves;
With the repeated multiple times washing of the hydrochloric acid of 1mol/L, remove washings, by organic phase solution concentrating under reduced pressure;
Add dissolve with methanol solution in enriched material, and with the repeated multiple times washing of normal hexane, merge n-hexane liquid;
In n-hexane liquid, add methanol solution, leave standstill, after complete layering, get methanol layer;
Methanol layer solution is concentrated obtains oily matter, and vacuum-drying at 38 DEG C, obtains type I compound;
Described formula II compound is 1:1.0 ~ 5.0 with the mol ratio of (+) DIP-Cl.
Wherein, (+) DIP-Cl refers to the compound with following structure:
。
Described (+) DIP-Cl directly needs buying according to purity, or according to the preparation method's preparation in existing open source literature.
Technical scheme disclosed in this invention, method one is simple to operate, and reaction conditions requires loose, and productive rate is higher; Method two only uses reductive agent, and corresponding solvent system, without the need to increasing other catalyzer, decreases raw material input cost, and requires loose to reaction conditions, without the need to the severe condition such as high temperature, high pressure, is suitable for suitability for industrialized production.
Embodiment
Embodiment 1
Adopt (S)-CBS-Me, dimethyl thioether reduction system reducing.
Chloro-1-(3, the 4-difluorophenyl of 42.64g 2-is added in 500ml there-necked flask) ethyl ketone (formula II compound, molecular weight 190.6; 0.224 mol; 1eq), 240ml anhydrous methylene chloride is added, stirring and dissolving, nitrogen protection.Be cooled to-11 DEG C, add 22 mL S-CBS toluene solutions (1M).Drip 29 ml borane dimethylsulf iotade (10M), about 10 min drip off, and dropping process keeps below-8 DEG C.Keep-5 ~ 0 DEG C.TLC follows the tracks of raw material completely dissolve.Drip 25ml methyl alcohol successively, drip the hydrogen peroxide of 102.5ml 6%, drip 72ml 2N sulfuric acid, hierarchy of control temperature is lower than 0 DEG C.Stirring at room temperature 30min is risen to after dripping off.Separatory, water layer dichloro hexane 300ml extracts, and merge organic layer, with saturated aqueous common salt, water washing, anhydrous sodium sulfate drying, concentrating under reduced pressure obtains oily matter 44.8g.Vacuum-drying at product 20 DEG C, obtains product 41.5g, yield 96.5%.
Embodiment 2
Adopt (+)-DIP-Cl reduction system reducing.
Chloro-1-(3, the 4-difluorophenyl of 10g 2-is added in reaction flask) ethyl ketone (formula II compound molecular weight 190.6,0.0524 mol, 1eq), and THF, stirring and dissolving.Nitrogen protection, 10 DEG C of instillation (+) DIP-Cl 41g (53%) 0.0682mol, drip off for about 10 minutes.Stirring at room temperature, it is complete that TLC monitors raw material reaction.The heavy 40g of system after evaporated under reduced pressure system solvent, add 50ml methylene dichloride to dissolve, with time washing of 1mol/L hydrochloric acid 50ml × 4, organic phase is spin-dried for heavy 30g and adds 50ml dissolve with methanol, time washing of normal hexane 50ml × 3, normal hexane is laminated and with the back extraction of 50ml methyl alcohol, methanol layer merges, and concentrating under reduced pressure obtains oily matter 12g.38 DEG C of vacuum are dry.Obtain 9.5g, yield 94%.
Comparative example 1
Adopt trimethoxy borine, S-diphenylprolinol, borine dme reduction system reducing (i.e. oxazole borane reduction system).
Under room temperature, trimethoxy borine 0.27g is added the toluene 13mL solution of the S-phenylbenzene Prolinol 0.47g through stirring.By this mixture in 40
otemperature is remained on 35 ~ 45 after stirring 90 minutes by C
oc, added borane dimethylsulf iotade 2.23g through 15 minutes.In 40
oc stirs 60 minutes, in 2 hours, then add chloro-1-(3, the 4-difluorophenyl of 7g 2-) the 18ml toluene solution of ethyl ketone (formula II compound).Dropwise, in 40
oc stirs 60 minutes, is then cooled to 10
oc.Methyl alcohol 10g is added in 20 minutes.Mixture is cooled to 20
oc, then stirs 30 minutes.Then, 45 are being no more than
obelow C concentrates, and washs 4 times, strip with toluene 20mL to obtained water layer with the aqueous acetic acid 28mL of 10% to toluene solution.Merge organic layer and use 15mL water washing.Concentration of organic layers obtains.38 DEG C of vacuum are dry.Obtain 5.0g, yield 71%.
By above experimental data, we can see, utilize two kinds of synthetic method yields disclosed in this invention far away higher than traditional reduction system.
And processing step disclosed in this invention is simple, without the need to the participation of a large amount of auxiliary reagent, is suitable for industrialization promotion.
Claims (2)
1. there is a synthetic method for optically active alcohol, described in there is optically active alcohol for compound shown in formula I,
(formula I),
It is characterized in that: described type I compound is formed through reduction by formula II,
(formula II),
Its concrete reactions steps is as follows:
(1) add in enough solvents by compound shown in formula II, described solvent is methylene dichloride;
(2) under nitrogen protection, abundant stirring and dissolving; Mixing solutions is cooled to-11 DEG C, adds the S-CBS-Me toluene solution of 1mol/L;
(3) drip the borane dimethylsulf iotade of 10mol/L, dropwise with the speed of 2.5 ~ 3ml/ min, in dropping process, keep system temperature lower than-8 DEG C;
(4) keep reaction system at-5 ~ 0 DEG C, utilize TLC to follow the tracks of, to raw material completely dissolve, drip successively methyl alcohol, 6% hydrogen peroxide and sulfuric acid, hierarchy of control temperature is lower than 0 DEG C; Stirring at room temperature 30min is risen to after dripping off;
(5) leave standstill, after solution layering, collect water layer and organic layer respectively;
(6) water layer dichloro hexane extracts, and by dichloro hexane extraction liquid and original machine also laminated;
(7) organic layer is used saturated aqueous common salt, water washing successively, then select anhydrous sodium sulfate drying, concentrating under reduced pressure obtains oily matter;
(8) oily matter vacuum-drying at 20 DEG C, obtains type I compound;
The mol ratio of described formula II compound and borane dimethylsulf iotade is 1:1.1 ~ 1.5; The amount ratio of described formula II compound and S-CBS-Me is the S-CBS-Me solution that 1mol formula II compound adds 5% ~ 15%.
2. there is a synthetic method for optically active alcohol, described in there is optically active alcohol for compound shown in formula I,
(formula I),
It is characterized in that: described type I compound is formed through reduction by formula II,
(formula II),
Its concrete reactions steps is as follows:
(1) add in enough solvents by compound shown in formula II, described solvent is tetrahydrofuran (THF);
(2) under nitrogen protection, abundant stirring and dissolving;
(3) under the temperature condition of 10 DEG C, drip (+) DIP-Cl, drop rate is 3.5 ~ 4.5g/min;
(4) keep reaction system at ambient temperature, utilize TLC to follow the tracks of, to raw material completely dissolve;
(5) evaporated under reduced pressure solution, adds methylene dichloride and dissolves;
(6) with the repeated multiple times washing of hydrochloric acid of 1mol/L, washings is removed, by organic phase solution concentrating under reduced pressure;
(7) add dissolve with methanol solution in enriched material, and with the repeated multiple times washing of normal hexane, merge n-hexane liquid;
(8) in n-hexane liquid, add methanol solution, leave standstill, after complete layering, get methanol layer;
(9) methanol layer solution is concentrated obtains oily matter, and vacuum-drying at 38 DEG C, obtains type I compound;
Described formula II compound is 1:1.0 ~ 5.0 with the mol ratio of (+) DIP-Cl.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310364510.2A CN103408399B (en) | 2013-08-21 | 2013-08-21 | A kind of synthetic method with optically active alcohol |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310364510.2A CN103408399B (en) | 2013-08-21 | 2013-08-21 | A kind of synthetic method with optically active alcohol |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103408399A CN103408399A (en) | 2013-11-27 |
| CN103408399B true CN103408399B (en) | 2015-09-16 |
Family
ID=49601458
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310364510.2A Active CN103408399B (en) | 2013-08-21 | 2013-08-21 | A kind of synthetic method with optically active alcohol |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103408399B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104974017B (en) * | 2014-04-09 | 2017-11-17 | 上海医药工业研究院 | The preparation method of (1R, 2S) 2 (3,4 difluorophenyl) cyclopropylamine D mandelates |
| CN107793330B (en) * | 2016-08-29 | 2020-03-17 | 鲁南制药集团股份有限公司 | Synthetic method of anacetrapib chiral intermediate |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4868344A (en) * | 1988-03-30 | 1989-09-19 | Aldrich-Boranes, Inc. | Novel process of producing phenyl or substituted phenylalkylamine pharmaceutical agents and novel chiral intermediates of high enantiomeric purity useful therein |
| CN102924457A (en) * | 2011-08-12 | 2013-02-13 | 上海恒瑞医药有限公司 | Triazolopyrimidine derivatives, preparation method and uses thereof |
| EP2589587A1 (en) * | 2011-11-04 | 2013-05-08 | Chemo Ibérica, S.A. | Synthesis of nitrogen substituted cyclopropanes |
-
2013
- 2013-08-21 CN CN201310364510.2A patent/CN103408399B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN103408399A (en) | 2013-11-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105348045B (en) | Method for synthesizing pentafluorophenol by using continuous flow reaction | |
| CN103601749B (en) | A kind of synthetic method of 1-alkyl pyrazole-4-pinacol borate | |
| CN103497233B (en) | Preparation method for bortezomib | |
| CN103408399B (en) | A kind of synthetic method with optically active alcohol | |
| CN105367526A (en) | Preparation method of high-purity n-butylphthalide | |
| CN102319550A (en) | Low-concentration viscoelastic surfactant solution and preparation method thereof | |
| CN104250236A (en) | Synthetic method of gamma-alkyl oxyacyl methyl-gamma-butyrolactone and delta- alkyl oxyacyl methyl-delta-valerolactone | |
| CN103204902A (en) | Aqueous-phase synthesis of novel key intermediate used for preparation of bortezomib and application of key intermediate in synthesis of bortezomib | |
| CN1326836C (en) | Lycopene purification preparation method | |
| CN104926785B (en) | A kind of selenium heteroaromatic ring derivative and preparation method thereof | |
| CN103664739B (en) | A kind of preparation method of Telaprevir intermediate | |
| CN103145746A (en) | Process method for synthesizing cyclopentene/ hexene-1-boronic acid pinacol cyclic ester | |
| CN102952169A (en) | Synthetic method of 6-methyl-17alpha-acetoxyl-19-norpregna-4,6-dialkyl-3,20-diketone | |
| CN105732298A (en) | Synthesis method of 1-bromo-9,9'-spirodifluorene | |
| CN110818765A (en) | Method for isomerizing cis-glycyrrhizic acid | |
| CN103214534A (en) | Preparation method of 3'-desoxyadenossine | |
| CN103896753B (en) | A kind of synthetic method of three grades of alpha-hydroxy carbonyl compounds | |
| CN103044192A (en) | Method for synthesizing luliconazole intermediate-(S)-2,4-dichloro-1-(1,2-dichloroethyl) benzene | |
| CN103435450B (en) | A kind of synthetic method of the TMHQ of environmental protection | |
| CN106543215A (en) | A kind of dinaphtho thiophene coughs up organic photoelectric functional material and its synthetic method | |
| CN103896834A (en) | 2-Cyano-3-cyclobutylpyridine and chemical synthesis method thereof | |
| CN105481684A (en) | Asymmetric synthesis method of dihydroartemisinic acid from arteannuinic acid | |
| CN102627571A (en) | Preparation and synthesis method for chiral ammonium salt | |
| CN103772269A (en) | Controllable preparation method of carbazole bromo-compound | |
| CN109503338A (en) | A method of preparing cis- trifluoromethyl styrene compound |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |