CN103483252B - Synthetic method of 2-cyclopropyl-4-(4-fluorophenyl)-3-quinolylmethanol - Google Patents
Synthetic method of 2-cyclopropyl-4-(4-fluorophenyl)-3-quinolylmethanol Download PDFInfo
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- CN103483252B CN103483252B CN201310396370.7A CN201310396370A CN103483252B CN 103483252 B CN103483252 B CN 103483252B CN 201310396370 A CN201310396370 A CN 201310396370A CN 103483252 B CN103483252 B CN 103483252B
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- cyclopropyl
- fluorophenyl
- quinoline
- sodium borohydride
- thf
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- 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
- C07D215/12—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 substituted hydrocarbon radicals attached to ring carbon atoms
- C07D215/14—Radicals substituted by oxygen atoms
Abstract
The invention discloses a synthetic method of 2-cyclopropyl-4-(4-fluorophenyl)-3-quinolylmethanol. The synthetic method comprises the following steps: reacting 2-cyclopropyl-4-(4-fluorophenyl)-quinoline-3-ethyl carboxylate, sodium borohydride, absolute ethyl alcohol and concentrated hydrochloric acid which are taken as raw materials in THF (Tetra Hydro Furan) to generate a diborane-THF solution, and reducing an ester carbonyl into an alcoholic hydroxyl by the diborane-THF solution taken as a reducing agent solution to obtain the 2-cyclopropyl-4-(4-fluorophenyl)-3-quinolylmethanol. The method provided by the invention is simple in operation steps, low in requirement for the desired equipment, low in energy consumption and short in reaction period; the product is high in purity and yield; the mass fraction of the product 2-cyclopropyl-4-(4-fluorophenyl)-3-quinolylmethanol obtained at last is above 98% and the yield of the same is above 95%, and therefore, the quality requirements of the market for the 2-cyclopropyl-4-(4-fluorophenyl)-3-quinolylmethanol at present are met.
Description
Technical field
The invention belongs to technical field of fine, relate to pharmaceutical chemicals synthetic technology, particularly a kind of 2-cyclopropyl-4-(4-fluorophenyl) synthetic method of-3-quinoline methanol.
Background technology
Pitavastatin Calcium is a kind of active drug for the treatment of hypercholesterolemia, Clinical practice is comparatively extensive, as the critical materials of synthesis Pitavastatin Calcium important intermediate (E)-3-[the fluoro-phenyl of 2-cyclopropyl-4-(4-)-3-quinolyl]-2 vinyl cyanide, 2-cyclopropyl-4-(4-fluorophenyl)-3-quinoline methanol plays an important role in synthesis, wide market.
Conventional hypolipidemic is as all difficult people's wills to the greatest extent of curative effect such as the special classes of nicotinic acid class, resene or shellfish, and effect for reducing fat is it is preferred that be called as the medicine of Statins.And the novel statins Pitavastatin Calcium developed by Kowa company in the recent period, the decreasing cholesterol effect good because of it and being called as " superstatin class medicine ".
The synthetic method of the pitavastatin of external report is more, although synthetic route is different, they utilizes common intermediate 2-cyclopropyl-4-(4-fluorophenyl)-3-quinoline methanol.At present, bibliographical information prepare 2-cyclopropyl-4-(4-fluorophenyl) method that-3-quinoline methanol is conventional has: (one) 2-cyclopropyl-4-(4-fluorophenyl)-quinoline-3-carboxylic acid ethyl ester adopts di-isopropyl aluminum hydride to reduce to obtain 2-cyclopropyl-4-(4-fluorophenyl)-3-quinoline methanol, and the weak point of the method is that total recovery is lower; (2) amino-4 '-fluoro-benzophenone of 2-and the condensation of 3-cyclopropyl-3-oxypropionitrile obtain 2-cyclopropyl-3-cyano group-4-(4'-fluorophenyl) quinoline, selective reduction cyano group is that hydroxyl obtains 2-cyclopropyl-4-(4-fluorophenyl)-3-quinoline methanol again, the weak point of the method is that cyano reduction is the yield only 30% ~ 40% of hydroxyl one step, and is difficult to purify; (3) 2-cyclopropyl-4-(4-fluorophenyl)-quinoline-3-carboxylic acid ethyl ester is directly through MgCl
2-KBH
42-cyclopropyl-4-(4-the fluorophenyl)-3-quinoline methanol of reduction system, its weak point is: (1) MgCl
2-KBH
4system is as reductive agent, and what work in reaction is the magnesium borohydride that both reactions generate, and its generation situation is not easy to detect, and is difficult to the amount determining the magnesium borohydride generated, and is difficult to separation and purification, partial double bond can be made in late phase reaction to be affected; (2) magnesium borohydride domestic market does not have finished product at present, and just in laboratory synthesis during use, magnesium borohydride runs into sky G&W vigorous reaction can occur, and releases a large amount of hydrogen and heat, requires harsher to reaction conditions.
Summary of the invention
For many deficiencies of prior art, the invention provides a kind of synthetic method of 2-cyclopropyl-4-(4-fluorophenyl)-3-quinoline methanol, with 2-cyclopropyl-4-(4-fluorophenyl)-quinoline-3-carboxylic acid ethyl ester for raw material, using sodium borohydride, dehydrated alcohol and concentrated hydrochloric acid for raw material reacts the diborane-THF solution of generation as reductant solution in THF, ester carbonyl group is reduced into alcoholic extract hydroxyl group, obtains 2-cyclopropyl-4-(4-fluorophenyl)-3-quinoline methanol.This synthetic method step is simple, and reaction conditions is gentle, and required equipment is less, and energy consumption is low, and reaction time is short, product purity and yield high.
Concrete synthetic route of the present invention is:
The synthetic method of 2-cyclopropyl-4-(4-fluorophenyl)-3-quinoline methanol of the present invention, with 2-cyclopropyl-4-(4-fluorophenyl)-quinoline-3-carboxylic acid ethyl ester for raw material, using sodium borohydride, dehydrated alcohol and concentrated hydrochloric acid for raw material reacts the diborane-THF solution of generation as reductant solution in THF, ester carbonyl group is reduced into alcoholic extract hydroxyl group, obtains 2-cyclopropyl-4-(4-fluorophenyl)-3-quinoline methanol.Concrete steps are:
(1) add in THF by sodium borohydride and dehydrated alcohol, continue heating, insulation backflow, obtains mixing solutions;
(2) under the described insulation backflow of step (1), the toluene solution of 2-cyclopropyl-4-(4-fluorophenyl)-quinoline-3-carboxylic acid ethyl ester is dissolved with to gained mixed solution and dripping, after being added dropwise to complete, continue heating, drip concentrated hydrochloric acid be incubated and stir, stopped reaction when adopting the massfraction <1% of HPLC monitoring 2-cyclopropyl-4-(4-fluorophenyl)-quinoline-3-carboxylic acid ethyl ester;
(3) pour step (2) gained reaction solution in frozen water cancellation, filter, separatory, aqueous phase extracted, merge organic phase, washing, reclaim under reduced pressure toluene, cooling, add sherwood oil again, stir, filter, dry, obtain white solid, i.e. target product 2-cyclopropyl-4-(4-fluorophenyl)-3-quinoline methanol.
Temperature of reaction described in step (1) is 70-84 ° of C, and soaking time is 5-6h.
Described in step (1), the mol ratio of sodium borohydride and dehydrated alcohol is 1:0.82.
Described step (1) is for preparing the preparation work of reductant solution, sodium borohydride and dehydrated alcohol are added after in THF, container sealing is intact, to prevent solution evaporation, heat temperature raising, solution presents white opacity, and pressed powder dissolves gradually, when being heated to 70-84 ° of C, carry out insulation reaction 5-6h.In this process, guarantee to be in anhydrous state, in case sodium borohydride water absorbent portion inactivation, cause sodium borohydride not react by full entry.
Described step (2) is first dissolved with the toluene solution of 2-cyclopropyl-4-(4-fluorophenyl)-quinoline-3-carboxylic acid ethyl ester to step (1) gained mixed solution and dripping, why by raw material 2-cyclopropyl-4-(4-fluorophenyl)-quinoline-3-carboxylic acid ethyl ester is dissolved in toluene, be because solubleness is high in 2-cyclopropyl-4-(4-fluorophenyl)-quinoline-3-carboxylic acid ethyl ester toluene morning, 2-cyclopropyl-4-(4-fluorophenyl)-quinoline-3-carboxylic acid ethyl ester can be made to participate in reaction completely as much as possible; After being added dropwise to complete, continuing heating, then drip concentrated hydrochloric acid.Like this, using sodium borohydride, dehydrated alcohol and concentrated hydrochloric acid for raw material reacts the diborane-THF solution of generation as reductant solution in THF.Here why selecting dehydrated alcohol, is because dehydrated alcohol toxicity is little, low price; Selective reaction generates diborane-tetrahydrofuran solution, is because diborane is volatile, easily contacts with air and form explosive mixture, and spontaneous combustion in damp atmosphere, there is severe toxicity.In addition, concentrated hydrochloric acid is dripped again after the toluene solution being dissolved with 2-cyclopropyl-4-(4-fluorophenyl)-quinoline-3-carboxylic acid ethyl ester is added dropwise to complete, its objective is that preventing the diborane generated from contacting with air forms explosive mixture and cause danger, also ensure that diborane participates in reaction completely simultaneously.
2-cyclopropyl-4-(4-fluorophenyl)-quinoline-3-carboxylic acid ethyl ester in described synthetic method: the mol ratio of toluene: sodium borohydride: THF is 1:8-12:1.4-1.6:3-5.
The molar weight adding sodium borohydride in described synthetic method is 1.4-1.6 times of described substrate 2-cyclopropyl-4-(4-fluorophenyl)-quinoline-3-carboxylic acid ethyl ester.If the add-on of sodium borohydride is very few, then the required reductive agent of reaction very little, thus it is even not thorough to cause the reaction times in later stage to extend; If the add-on of sodium borohydride is too much, then residual sodium borohydride in the solution is easily met the angry body of aquatic products and is caused danger when later stage separating treatment, also can cause wastage of material.
The massfraction of step (2) described concentrated hydrochloric acid is 37.5%.
In described synthetic method, the mol ratio of sodium borohydride and concentrated hydrochloric acid is 1:1.1.Because concentrated hydrochloric acid understands some volatilization in container in dropping process, so make concentrated hydrochloric acid excessive a little.Like this, in scope described above, the needs of reaction can be met, turn avoid the waste of raw material.
Step (2) described temperature of reaction is 95-105 ° of C, soaking time 6-8 h.
In described step (2) process, be dissolved with the toluene solution of 2-cyclopropyl-4-(4-fluorophenyl)-3-quinoline carboxylic acid ethyl ester to the mixed solution and dripping of gained under the described insulation backflow of step (1), after being added dropwise to complete, continuing heat temperature raising makes THF steam recovery, is warming up to 95-105 ° of C, drips concentrated hydrochloric acid and is incubated and stirs, insulation reaction 6-8 h, reaction solution, in becoming grey black gradually by orange red, is noted sealing, is prevented solution evaporation in insulation reaction process.
In order to keep the quality of target product, the described washing of step (3) adopts saturated aqueous common salt, and its object has: (1) prevents emulsification; (2) solubleness of target product 2-cyclopropyl-4-(4-fluorophenyl)-3-quinoline methanol in water is reduced; (3) by product sodium salt is washed away.
Step (3) described cooling temperature is 5-10 ° of C.
The time of step (3) described stirring is 1-2 h.
In sum, the invention provides a kind of synthetic method of 2-cyclopropyl-4-(4-fluorophenyl)-3-quinoline methanol, the method, is reacted as reductant solution using the diborane-THF solution that sodium borohydride, dehydrated alcohol and concentrated hydrochloric acid react generation for raw material in THF for starting raw material with 2-cyclopropyl-4-(4-fluorophenyl)-quinoline-3-carboxylic acid ethyl ester.The method operation steps is simple, required equipment is less, energy consumption is low, reaction time is short, purity and the yield of product are high, the massfraction of product 2-cyclopropyl-4-(4-the fluorophenyl)-3-quinoline methanol finally obtained is more than 98%, and yield, more than 96%, meets in the market to the specification of quality of 2-cyclopropyl-4-(4-fluorophenyl)-3-quinoline methanol.
Embodiment
Raw material of the present invention is commercially available prod.
Embodiment 1
A kind of 2-cyclopropyl-4-(4-fluorophenyl) synthetic method of-3-quinoline methanol, its concrete steps are:
(1) 4.93g sodium borohydride and 6.24mL dehydrated alcohol are added in 21.08mL THF, be heated to 70 DEG C, insulation backflow 5h, obtains mixing solutions;
(2) under the described insulation backflow of step (1), the toluene solution 73.77mL of 29.10g 2-cyclopropyl-4-(4-fluorophenyl)-quinoline-3-carboxylic acid ethyl ester is dissolved with to gained mixed solution and dripping, after being added dropwise to complete, continue to be heated to 100 DEG C, the concentrated hydrochloric acid that dropping volume is 4.42mL, massfraction is 37.5% is incubated and stirs 8h, stopped reaction when adopting HPLC to monitor the massfraction <1% of 2-cyclopropyl-4-(4-fluorophenyl)-quinoline-3-carboxylic acid ethyl ester;
(3) pour step (2) gained reaction solution in frozen water cancellation, filter, separatory, aqueous phase extracted, merges organic phase, saturated common salt water washing, reclaim under reduced pressure toluene under 0.1MPa, is cooled to 5 DEG C, then adds sherwood oil, stir 1h, filtration, 50 DEG C of oven dry, obtain white solid, i.e. target product 2-cyclopropyl-4-(4-fluorophenyl)-3-quinoline methanol, massfraction is 98.99%, and yield is 96.33%.
Embodiment 2
A kind of 2-cyclopropyl-4-(4-fluorophenyl) synthetic method of-3-quinoline methanol, its concrete steps are:
(1) 5.31g sodium borohydride and 6.72mL dehydrated alcohol are added in 28.38mL THF, be heated to 80 DEG C, insulation backflow 6h, obtains mixing solutions;
(2) under the described insulation backflow of step (1), the toluene solution 93.10mL of 29.34g 2-cyclopropyl-4-(4-fluorophenyl)-quinoline-3-carboxylic acid ethyl ester is dissolved with to gained mixed solution and dripping, after being added dropwise to complete, continue to be heated to 95 DEG C, the concentrated hydrochloric acid that dropping volume is 4.76mL, massfraction is 37.5% is incubated and stirs 7h, stopped reaction when adopting HPLC to monitor the massfraction <1% of 2-cyclopropyl-4-(4-fluorophenyl)-quinoline-3-carboxylic acid ethyl ester;
(3) pour step (2) gained reaction solution in frozen water cancellation, filter, separatory, aqueous phase extracted, merges organic phase, saturated common salt water washing, reclaim under reduced pressure toluene under 0.1MPa, is cooled to 10 DEG C, then adds sherwood oil, stir 2h, filtration, 50 DEG C of oven dry, obtain white solid, i.e. target product 2-cyclopropyl-4-(4-fluorophenyl)-3-quinoline methanol, massfraction is 99.55%, and yield is 96.11%.
Embodiment 3
A kind of 2-cyclopropyl-4-(4-fluorophenyl) synthetic method of-3-quinoline methanol, its concrete steps are:
(1) 7.59g sodium borohydride and 9.61mL dehydrated alcohol are added in 57.93mL THF, be heated to 84 DEG C, insulation backflow 5.5h, obtains mixing solutions;
(2) under the described insulation backflow of step (1), the toluene solution 182.45mL of 47.91g 2-cyclopropyl-4-(4-fluorophenyl)-quinoline-3-carboxylic acid ethyl ester is dissolved with to gained mixed solution and dripping, after being added dropwise to complete, continue to be heated to 105 DEG C, the concentrated hydrochloric acid that dropping volume is 6.80mL, massfraction is 37.5% is incubated and stirs 6h, stopped reaction when adopting HPLC to monitor the massfraction <1% of 2-cyclopropyl-4-(4-fluorophenyl)-quinoline-3-carboxylic acid ethyl ester;
(3) pour step (2) gained reaction solution in frozen water cancellation, filter, separatory, aqueous phase extracted, merges organic phase, saturated common salt water washing, reclaim under reduced pressure toluene under 0.1MPa, is cooled to 8 DEG C, then adds sherwood oil, stir 1.5h, filtration, 50 DEG C of oven dry, obtain white solid, i.e. target product 2-cyclopropyl-4-(4-fluorophenyl)-3-quinoline methanol, massfraction is 98.99%, and yield is 96.5%.
Embodiment 4
A kind of 2-cyclopropyl-4-(4-fluorophenyl) synthetic method of-3-quinoline methanol, its concrete steps are:
(1) 6.82g sodium borohydride and 8.63ml dehydrated alcohol are added in 38.93mL THF, be heated to 75 DEG C, insulation backflow 5h, obtains mixing solutions;
(2) under the described insulation backflow of step (1), the toluene solution 114.91mL of 40.24g 2-cyclopropyl-4-(4-fluorophenyl)-quinoline-3-carboxylic acid ethyl ester is dissolved with to gained mixed solution and dripping, after being added dropwise to complete, continue to be heated to 98 DEG C, the concentrated hydrochloric acid that dropping volume is 6.12mL, massfraction is 37.5% is incubated and stirs 7.5h, stopped reaction when adopting HPLC to monitor the massfraction <1% of 2-cyclopropyl-4-(4-fluorophenyl)-quinoline-3-carboxylic acid ethyl ester;
(3) pour step (2) gained reaction solution in frozen water cancellation, filter, separatory, aqueous phase extracted, merges organic phase, saturated common salt water washing, reclaim under reduced pressure toluene under 0.1MPa, is cooled to 6 DEG C, then adds sherwood oil, stir 2h, filtration, 50 DEG C of oven dry, obtain white solid, i.e. target product 2-cyclopropyl-4-(4-fluorophenyl)-3-quinoline methanol, massfraction is 99.01%, and yield is 96.52%.
As can be seen from embodiment 1-4, adopt the method for the invention synthesis 2-cyclopropyl-4-(4-fluorophenyl)-3-quinoline methanol, operation steps is simple, required equipment is less, and energy consumption is low, and reaction time is short, purity and the yield of product are high, the massfraction of product 2-cyclopropyl-4-(4-the fluorophenyl)-3-quinoline methanol finally obtained is more than 98%, and yield, more than 96%, meets in the market to the specification of quality of 2-cyclopropyl-4-(4-fluorophenyl)-3-quinoline methanol.
Claims (1)
1. the synthetic method of 2-cyclopropyl-4-(4-fluorophenyl)-3-quinoline methanol, it is characterized in that: with 2-cyclopropyl-4-(4-fluorophenyl)-quinoline-3-carboxylic acid ethyl ester for raw material, using sodium borohydride, dehydrated alcohol and concentrated hydrochloric acid for raw material reacts the diborane-THF solution of generation as reductant solution in THF, ester carbonyl group is reduced into alcoholic extract hydroxyl group, obtains 2-cyclopropyl-4-(4-fluorophenyl)-3-quinoline methanol;
Concrete steps are:
(1) add in THF by sodium borohydride and dehydrated alcohol, heating, insulation backflow, obtains mixing solutions;
(2) under the described insulation backflow of step (1), the toluene solution of 2-cyclopropyl-4-(4-fluorophenyl)-quinoline-3-carboxylic acid ethyl ester is dissolved with to gained mixed solution and dripping, after being added dropwise to complete, continue heating, drip concentrated hydrochloric acid be incubated and stir, stopped reaction when adopting the massfraction <1% of HPLC monitoring 2-cyclopropyl-4-(4-fluorophenyl)-quinoline-3-carboxylic acid ethyl ester;
(3) pour step (2) gained reaction solution in frozen water cancellation, filter, separatory, aqueous phase extracted, merge organic phase, washing, reclaim under reduced pressure toluene, cooling, add sherwood oil again, stir, filter, dry, obtain white solid, i.e. target product 2-cyclopropyl-4-(4-fluorophenyl)-3-quinoline methanol;
Temperature of reaction described in step (1) is 70-84 ° of C, and soaking time is 5-6h;
Described in step (1), the mol ratio of sodium borohydride and dehydrated alcohol is 1:0.82;
2-cyclopropyl-4-(4-fluorophenyl)-quinoline-3-carboxylic acid ethyl ester in described synthetic method: the mol ratio of toluene: sodium borohydride: THF is 1:8-12:1.4-1.6:3-5;
In described synthetic method, the mol ratio of sodium borohydride and concentrated hydrochloric acid is 1:1.1;
The hydrochloric acid of step (2) described use for massfraction be the concentrated hydrochloric acid of 37.5%;
Step (2) described temperature of reaction is 95-105 ° of C, soaking time 6-8 h.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0304063A2 (en) * | 1987-08-20 | 1989-02-22 | Nissan Chemical Industries Ltd. | Quinoline type mevalonolactones |
| CN1951920A (en) * | 2005-10-21 | 2007-04-25 | 上海医药工业研究院 | Process for preparing 4-(4-fluoro-phenyl)-3- hydroxymethyl-2- cyclopropyl-quinoline |
| CN101747265A (en) * | 2008-12-11 | 2010-06-23 | 上海医药工业研究院 | Method for preparing 2-cyclopropyl-4-(4'-fluorophenyl) quinoline-3-methanol |
-
2013
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0304063A2 (en) * | 1987-08-20 | 1989-02-22 | Nissan Chemical Industries Ltd. | Quinoline type mevalonolactones |
| CN1951920A (en) * | 2005-10-21 | 2007-04-25 | 上海医药工业研究院 | Process for preparing 4-(4-fluoro-phenyl)-3- hydroxymethyl-2- cyclopropyl-quinoline |
| CN101747265A (en) * | 2008-12-11 | 2010-06-23 | 上海医药工业研究院 | Method for preparing 2-cyclopropyl-4-(4'-fluorophenyl) quinoline-3-methanol |
Non-Patent Citations (2)
| Title |
|---|
| 烃基硼烷在有机合成中的应用;黄宪;《化学通报》;19771231(第4期);第28页左栏第2段、反应式 * |
| 闻韧.《药物合成反应》.《药物合成反应》.2003,第364页. * |
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