CN108299156A - A kind of new synthetic method of luliconazole key chiral intermediate - Google Patents
A kind of new synthetic method of luliconazole key chiral intermediate Download PDFInfo
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- CN108299156A CN108299156A CN201810230404.8A CN201810230404A CN108299156A CN 108299156 A CN108299156 A CN 108299156A CN 201810230404 A CN201810230404 A CN 201810230404A CN 108299156 A CN108299156 A CN 108299156A
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- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/132—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group
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- C07C29/143—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of ketones
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- C07C17/16—Preparation of halogenated hydrocarbons by replacement by halogens of hydroxyl groups
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Abstract
The invention discloses a kind of new synthetic methods of luliconazole key chiral intermediate, belong to the field of chemical synthesis.The invention is to first pass through preparation (R) 2 halogenated 1 (2,4 dichlorophenyls) ethyl alcohol, then hydroxyl carried out halogenated, then obtain the crucial chiral intermediate (S) 2 of synthesis luliconazole, 4 dichloro 1 (1,2 dihalo ethyl) benzene.The method is completed preparing chiral alcohol in water phase, without using organic solvent, reduces harm of the organic solvent to environment；Chiral catalyst demand used is few, and the catalyst can realize recycling under extraction conditions, greatly reduce reaction cost；Simultaneously the yield of final product (S) 2,4 dichloro 1 (1,2 dihalo ethyl) benzene can in this way improved, utilize industrial applications.
Description
Technical field
It is newly square that the present invention relates to the field of chemical synthesis more particularly to a kind of synthesis of luliconazole key chiral intermediate
Method.
Background technology
Luliconazole is the imidazoles antifungal drug of Nihon Nihyaku Co., Ltd's exploitation, this medicine is obtained in June, 2005
Approval is listed from 20 days July in 2005 with trade name Le リ Us Application (Lulicon).The principal indication of luliconazole is tinea pedis
The incidence of (i.e. athlete's foot), the disease is very high, and compared with previous antimycotic externally applied drug, the maximum advantage of luliconazole is skin
Rate height is stored, medication cycle is short (for the half of general drug), good effect and uneasy to recur, therefore has prodigious competitiveness.
But crucial chiral intermediate (S) -2,4- two chloro- 1- (1,2- dihalos ethyl) benzene of luliconazole is synthesized at present
It prepares there is not yet document report, and prepares (S) -2, the important link of bis- chloro- 1- of 4- (1,2- dihalo ethyl) benzene is exactly (R) -
The preparation of the halogenated -1- of 2- (2,4 dichloro benzene base) ethyl alcohol or the like.Wherein, representative synthetic route mainly have with
Lower two：
The report in document " Bioorganic＆Medicinal Chemistry Letters 2005,15,2749-2751 "
Road prepares (R)-using expensive chirality (-)-DIP-Cl as borane reagent in the presence of -25 DEG C, tetrahydrofuran solvent
Halogenated-the 1- of 2- (2,4 dichloro benzene base) alcohol product.The product synthesized using the route is difficult to realize the separation with product, to production
Product purifying creates great difficulties, and product yield is low；Meanwhile the reaction makees solvent with tetrahydrofuran and chiral reagent is difficult to realize follow
Ring recycles, and considerably increases production cost, it is difficult to further carry out industrial applications.
It is reported in document " J.Org.Chem.2011,76,2115-2122 " and utilizes expensive carbonyl reductase T
And coenzyme come assist complete (R) -2- halogenated -1- (2,4 dichloro benzene base) alcohol product preparation.In the route, carbonyl reductase
T usage amounts are big, while the concentration of substrate is low, need to realize volume production using the equipment of significant volume, can cause raw material in this way
And equipment cost is high, is unfavorable for further industrialized production.
Invention content
The present invention's is：In view of the above problems, a kind of synthesis of luliconazole key chiral intermediate is provided
New method, the method sintetics is at low cost, and reaction condition is mild, and new process is environmental-friendly, is truly realized Green Chemistry, together
When the present invention yield of luliconazole key chiral intermediate can be made to increase.
The technical solution adopted by the present invention is as follows：
A kind of new synthetic method of luliconazole key chiral intermediate, new synthetic method route are：
Wherein X is one kind in Cl, Br, specifically includes two steps：
A, the preparation of the halogenated -1- of (R) -2- (2,4 dichloro benzene base) ethyl alcohol：
By chiral catalyst, water (de aerated water), surfactant/phase transfer catalyst, hydrogen source, the halogenated -2,4- dichloros of ω -
Acetophenone I is added sequentially in reaction bulb, and reaction temperature is 11 DEG C -69 DEG C, and reaction time 7-19h, reaction finishes, and extraction is added
Agent is taken, product, desiccant dryness are extracted, filtering is concentrated to dryness, then the extractant of equivalent is added to carry out cooling crystallization to get white
Color solid (R) -2- halogenated -1- (2,4 dichloro benzene base) ethyl alcohol；
B, two chloro- 1- of (S) -2,4- (1,2- dihalos ethyl) benzene
In three-necked flask, (R) -2- halogenated -1- (2,4- dichlorophenyl) ethyl alcohol, dichloromethane, solvent, cooling is added
10-15 DEG C, halogen source object is added dropwise, 4h is dripped off, and is warming up to 11-49 DEG C, reacts 11-49h, water quenching is added to go out；It is extracted with extractant,
It is dry, it filters, concentration obtains bis- chloro- 1- of luliconazole key chiral intermediate (S) -2,4- (1,2- dihalo ethyl) benzene.
Specifically, preferably 20~40 DEG C of the reaction temperature of the step A, reaction time are preferably 8~15 hours；The B
Preferably 20~30 DEG C of step reaction temperature, the reaction time is preferably 20~30 hours.
Chiral catalyst described in the step A is chiral ligand (S, S)-N- to Methyl benzenesulfonyl base -1,2- diphenyl
The complex compound that ethylenediamine is formed with transition metal；The transition metal is one kind in ruthenium, rhodium, iridium, preferably ruthenium.
Specifically, the transition metal complex precursor is [Ru (p-cymene) Cl2]2、[Cp*RhCl2]2Or [Cp*
IrCl2]2In one kind.
Surfactant described in the step A includes cationic surface active agent, anionic surfactant, double
Ionic surfactant, nonionic surface active agent.
Further, the cationic surface active agent includes three alkane of cetyl trimethylammonium bromide and myristyl
At least one of base ammonium bromide；The anionic surfactant includes lauryl sodium sulfate, myristyl sodium sulfonate
At least one of with sodium cetanesulfonate；The double ion type surfactant includes three alkane of cetyl of sulfonic acid substitution
At least one of the myristyl trialkylammonium bromide of base ammonium bromide and sulfonic acid substitution；The nonionic surface active agent packet
Include at least one of polyethylene glycol -100, polyethylene glycol-400, Polyethylene glycol-2000, polyethylene glycol-1000 0 and cyclodextrin.
Phase transfer catalyst described in the step A is crown ether-like phase transfer catalysts and quaternary ammonium salt-type phase transfer catalyst
In one kind.
Further, the crown ether-like phase transfer catalysts are one kind in 15- crown-s 5 and 18- crown-s 6；The quaternary ammonium salt
Class phase transfer catalyst is one kind in tetra-alkyl ammonium chloride, tetraalkyl ammonium bromide or tetraalkylammonium iodides.
Hydrogen source described in the step A is one in sodium formate, two aqueous sodium bicarbonates, ammonium formate and formic acid/triethylamine
Kind.
Extractant described in the step A is one kind in benzene, toluene, ether, hexane and hexamethylene, preferably hexamethylene；
Extractant in the step B is one kind in chloroform, methyl tertiary butyl ether(MTBE), dichloromethane, preferably dichloromethane.
The drier is at least one of anhydrous sodium sulfate, anhydrous magnesium sulfate, activated carbon and anhydrous calcium chloride.
Halogen source object described in the step B is one kind in oxalyl chloride, bromine, (R) -2- halogenated -1- (2,4- dichloro-benzenes
Base) molar ratio of ethyl alcohol and oxalyl chloride/bromine is 1: 2~1: 8, preferably 1:3-1：6.
ω-described in the step A is halogenated-and the molar ratio of 2,4 dichloro benzene ethyl ketone and chiral catalyst is 50: 1~300:
1, preferably 50: 1~100: 1；The ω-is halogenated -2,4 dichloro benzene ethyl ketone and surfactant or mole of phase transfer catalyst
Than being 5: 1~30: 1, preferably 8: 1~15: 1；The ω-is halogenated-and the molar ratio of 2,4 dichloro benzene ethyl ketone and hydrogen source is 1: 3~1:
20, preferably 1: 5~1: 10.
In conclusion by adopting the above-described technical solution, the beneficial effects of the invention are as follows：Due to skill using the present invention
Art scheme, the method sintetics is at low cost, and reaction condition is mild, and new process is environmental-friendly, is truly realized Green Chemistry, can
Strong operability is easy to industrialized production；The present invention can make the yield of luliconazole key chiral intermediate increase simultaneously,
With ω-it is halogenated -2,4- dichloroacetophenones be standard, mole total recovery >=90.0%, final products optical purity >=99.0%.
Description of the drawings
Examples of the present invention will be described by way of reference to the accompanying drawings, wherein：
Fig. 1 is the synthetic route chart of (S) -2,4- two chloro- 1- (1,2- dihalos ethyl) benzene.
Specific implementation mode
All features disclosed in this specification or disclosed all methods or in the process the step of, in addition to mutually exclusive
Feature and/or step other than, can combine in any way.
Any feature disclosed in this specification (including any accessory claim, abstract), unless specifically stated,
It is replaced by other equivalent or with similar purpose alternative features.That is, unless specifically stated, each feature is a series of
An example in equivalent or similar characteristics.
Embodiment 1
(R) synthesis of the chloro- 1- of -2- (2,4 dichloro benzene base) ethyl alcohol
Under nitrogen protection, by 0.31 gram of ruthenium complex precursor [Ru (p-cymene) Cl2]2With 0.67 gram it is optically pure (S,
S)-N- is added in 250 milliliters of reaction bulbs Methyl benzenesulfonyl base -1,2- diphenyl ethylene diamine, adds 100 milliliters of de aerated water,
35-40 DEG C is heated to react 1 hour；Add 0.25 gram of cetyl trimethylammonium bromide, 52 grams of NaHCO3·2H2O and
22 grams of ω-chloro -2,4- dichloroacetophenone, reaction temperature are 25-35 DEG C, and it is 14 hours to keep the thermotonus, has been reacted
Bi Hou, with n-hexane extraction product, extract liquor is dried with anhydrous sodium sulfate, filters out sodium sulphate, is concentrated to dryness；Add 55 millis
The n-hexane risen dissolves by heating, then is down to room temperature crystallization, filters, dries (R) -2- chloro- 1- (2,4- dichlorophenyl) ethyl alcohol
21.2 grams, optical purity 99.2%.
The recycling of catalyst
When the first step after completion of the reaction, after going out product with n-hexane extraction, water phase is transferred in 250 milliliters of reaction bulb,
Under nitrogen protection, 22 grams of ω-chloro -2,4- dichloroacetophenone is added, and adds 4.1 milliliters of formic acid, at 25-35 DEG C
Under, stoichiometric number ten hours；Reaction finishes, other operations are the same as above-mentioned.
The recycling situation of chiral catalyst：
A. the conversion ratio of raw material ω-chloro -2,4- dichloroacetophenone is detected by HPLC and is determined；
B. the optical purity for two chloro- 1- (1,2- Dichloroethyls) benzene of product (S) -2,4- not recrystallized.
Embodiment 2
(R) synthesis of the chloro- 1- of -2- (2,4 dichloro benzene base) ethyl alcohol
Under nitrogen protection, by 0.15 gram of ruthenium complex precursor [Ru (p-cymene) Cl2]2With 0.34 gram it is optically pure (S,
S)-N- is added in 150 milliliters of reaction bulbs Methyl benzenesulfonyl base -1,2- diphenyl ethylene diamine, adds 60 milliliters of de aerated water, adds
Heat is to 35-40 DEG C；0.12 gram of cetyl trimethylammonium bromide, 26 grams of NaHCO is added in reaction after 1 hour3·2H2O and 11
Gram ω-chloro -2,4- dichloroacetophenone, reaction temperature be 25-35 DEG C, keep the thermotonus 12 hours；N-hexane is added
Product is extracted, extract liquor is dried with anhydrous sodium sulfate, filters out sodium sulphate, is concentrated to dryness, and 30 milliliters of n-hexane is added
It dissolves by heating, then is down to room temperature crystallization, filter, dry 10.6 grams of (R) -2- chloro- 1- (2,4- dichlorophenyl) ethyl alcohol, optical voidness
Degree 99.3%.
Embodiment 3
(R) synthesis of the chloro- 1- of -2- (2,4 dichloro benzene base) ethyl alcohol
Under nitrogen protection, by 0.15 gram of ruthenium complex precursor [Ru (p-cymene) Cl2]2With 0.34 gram it is optically pure (S,
S)-N- is added in 150 milliliters of reaction bulbs Methyl benzenesulfonyl base -1,2- diphenyl ethylene diamine, adds 60 milliliters of de aerated water, adds
Heat is to 35-40 DEG C；0.54 gram of lauryl sodium sulfate, 26 grams of NaHCO is added in reaction after 1 hour3·2H2O and 11 gram
ω-chloro -2,4- dichloroacetophenone, reaction temperature are 25-35 DEG C, keep the thermotonus 12 hours, reaction finishes；It is added just
Hexane extracts product, and extract liquor is dried with anhydrous sodium sulfate, filters out sodium sulphate, is concentrated to dryness, and is adding 30 milliliters just
Hexane dissolves by heating, then is down to room temperature crystallization, filters, dries 10.5 grams of (R) -2- chloro- 1- (2,4- dichlorophenyl) ethyl alcohol, light
Learn purity 99.1%.
Embodiment 4
(R) synthesis of the chloro- 1- of -2- (2,4 dichloro benzene base) ethyl alcohol
Under nitrogen protection, by 0.15 gram of ruthenium complex precursor [Ru (p-cymene) Cl2]2With 0.34 gram it is optically pure (S,
S)-N- is added in 150 milliliters of reaction bulbs Methyl benzenesulfonyl base -1,2- diphenyl ethylene diamine, adds 60 milliliters of de aerated water, adds
Heat is to 35-40 DEG C；Reaction is added 0.4 milliliter 15- crown-s 5 after 1 hour are used as phase transfer catalyst, 26 grams of NaHCO3·2H2O
With 11 grams of ω-chloro -2,4- dichloroacetophenone, reaction temperature is 25-35 DEG C, keeps the thermotonus 12 hours, has reacted
Finish；N-hexane extraction is added and goes out product, extract liquor is dried with anhydrous sodium sulfate, filters out sodium sulphate, is concentrated to dryness, and adds 30
The n-hexane of milliliter dissolves by heating, then is down to room temperature crystallization, filters, dries (R) -2- chloro- 1- (2,4- dichlorophenyl) ethyl alcohol
10.4 grams, optical purity 98.9%.
Embodiment 5
(R) synthesis of the chloro- 1- of -2- (2,4 dichloro benzene base) ethyl alcohol
Under nitrogen protection, by 0.32 gram of rhodium complex precursor [Cp*RhCl2]2With-N- pairs of 0.67 gram optically pure (S, S)
Methyl benzenesulfonyl base -1,2- diphenyl ethylene diamine is added in 250 milliliters of reaction bulbs, is added 120 milliliters of de aerated water, is heated to
35-40℃；0.24 gram of cetyl trimethylammonium bromide, 52 grams of NaHCO is added in reaction after 1 hour3·2H2O and 22 gram
ω-chloro -2,4- dichloroacetophenone, reaction temperature are 25-35 DEG C, keep the thermotonus 14 hours, reaction finishes；It is added just
Hexane extracts product, and extract liquor is dried with anhydrous sodium sulfate, filters out sodium sulphate, is concentrated to dryness, and is adding 50 milliliters just
Hexane dissolves by heating, then is down to room temperature crystallization, filters, dries 21.0 grams of (R) -2- chloro- 1- (2,4- dichlorophenyl) ethyl alcohol, light
Learn purity 99.0%.
Embodiment 6
(R) synthesis of the chloro- 1- of -2- (2,4 dichloro benzene base) ethyl alcohol
Under nitrogen protection, by 0.4 gram of rhodium complex precursor [Cp*IrCl2]2With-N- pairs of 0.67 gram optically pure (S, S)
Methyl benzenesulfonyl base -1,2- diphenyl ethylene diamine is added in 250 milliliters of reaction bulbs, is added 120 milliliters of de aerated water, is heated to
35-40℃；0.24 gram of cetyl trimethylammonium bromide, 52 grams of NaHCO is added in reaction after 1 hour3·2H2O and 22 gram
ω-chloro -2,4- dichloroacetophenone, reaction temperature are 25-35 DEG C, keep the thermotonus 14 hours, reaction finishes；It is added just
Hexane extracts product, and extract liquor is dried with anhydrous sodium sulfate, filters out sodium sulphate, is concentrated to dryness, and is adding 50 milliliters just
Hexane dissolves by heating, then is down to room temperature crystallization, filters, dries 19.7 grams of (R) -2- chloro- 1- (2,4- dichlorophenyl) ethyl alcohol, light
Learn purity 98.2%.
Embodiment 7
(S) synthesis of two chloro- 1- of -2,4- (1,2- Dichloroethyls) benzene
Under 1L there-necked flasks, nitrogen protection, be added 25 grams (R) -2- chloro- 1- (2,4- dichlorophenyl) ethyl alcohol, 250 milliliters
Dichloromethane, 20 grams of DMF dissolving, temperature is down to 10-15 DEG C.The molten of 300 milliliters of dichloromethane of 40 grams of oxalyl chlorides is added dropwise
Liquid drips off for about 4 hours；Drop finishes, natural temperature reaction, reacts 12 hours at room temperature；Water quenching is added to go out reaction, uses dichloromethane
Alkane extracts product, and activated carbon is added, and after dried over sodium sulfate, filters out sodium sulphate, is concentrated under reduced pressure solvent, obtains product (S)-
25. grams of 2,4- bis- chloro- 1- (1,2- Dichloroethyls) benzene, yield 95.3%.
Embodiment 8
(S) synthesis of two chloro- 1- of -2,4- (1,2- Dichloroethyls) benzene
Under 2L there-necked flasks, nitrogen protection, be added 50 grams (R) -2- chloro- 1- (2,4- dichlorophenyl) ethyl alcohol, 500 milliliters
Dichloromethane, 39 grams of DMF dissolving, temperature is down to 10-15 DEG C.The molten of 500 milliliters of dichloromethane of 57 grams of oxalyl chlorides is added dropwise
Liquid drips off for about 6 hours；Drop finishes, natural temperature reaction, reacts 14 hours at room temperature；Water quenching is added to go out reaction, uses dichloromethane
Alkane extracts product, and activated carbon is added, and after dried over sodium sulfate, filters out sodium sulphate, is concentrated under reduced pressure solvent, obtains product (S)-
51.3 grams of 2,4- bis- chloro- 1- (1,2- Dichloroethyls) benzene, yield 95.0%.
The invention is not limited in specific implementation modes above-mentioned.The present invention, which expands to, any in the present specification to be disclosed
New feature or any new combination, and disclose any new method or process the step of or any new combination.
Claims (11)
1. a kind of new synthetic method of luliconazole key chiral intermediate, which is characterized in that new synthetic method route is：
Wherein X is one kind in Cl, Br, specifically includes two steps：
A, the preparation of the halogenated -1- of (R) -2- (2,4 dichloro benzene base) ethyl alcohol：
By chiral catalyst, water (de aerated water), surfactant/phase transfer catalyst, hydrogen source, ω-it is halogenated -2,4 dichloro benzene second
Ketone I is added sequentially in reaction bulb, and reaction temperature is 11 DEG C -69 DEG C, and reaction time 7-19h, reaction finishes, and extraction is added
Agent extracts product, desiccant dryness, and filtering is concentrated to dryness, then the extractant of equivalent is added to carry out cooling crystallization to get white
Solid (R) -2- halogenated -1- (2,4 dichloro benzene base) ethyl alcohol；
B, two chloro- 1- of (S) -2,4- (1,2- dihalos ethyl) benzene
In three-necked flask, (R) -2- halogenated -1- (2,4- dichlorophenyl) ethyl alcohol, dichloromethane is added, solvent, cool down 10-15
DEG C, halogen source object is added dropwise, 4h is dripped off, and is warming up to 11-49 DEG C, reacts 11-49h, water quenching is added to go out；It is extracted with extractant, it is dry,
Filtering, concentration, obtains bis- chloro- 1- of luliconazole key chiral intermediate (S) -2,4- (1,2- dihalo ethyl) benzene.
2. a kind of new synthetic method of luliconazole key chiral intermediate as described in claim 1, which is characterized in that described
Chiral catalyst described in step A is chiral ligand (S, S)-N- to Methyl benzenesulfonyl base -1,2- diphenyl ethylene diamines and transition
The complex compound that metal is formed；The transition metal is one kind in ruthenium, rhodium, iridium, preferably ruthenium.
3. a kind of new synthetic method of luliconazole key chiral intermediate as described in claim 1, which is characterized in that described
Surfactant described in step A includes cationic surface active agent, anionic surfactant, the work of double ion type surface
Property agent, nonionic surface active agent.
4. a kind of new synthetic method of luliconazole key chiral intermediate as claimed in claim 3, which is characterized in that described
Cationic surface active agent includes at least one of cetyl trimethylammonium bromide and myristyl trialkylammonium bromide；
The anionic surfactant include in lauryl sodium sulfate, myristyl sodium sulfonate and sodium cetanesulfonate extremely
Few one kind；The double ion type surfactant includes the ten of the cetyl trialkylammonium bromide that sulfonic acid replaces and sulfonic acid substitution
At least one of tetraalkyl trialkylammonium bromide；The nonionic surface active agent includes polyethylene glycol -100, poly- second two
At least one of alcohol -400, Polyethylene glycol-2000, polyethylene glycol-1000 0 and cyclodextrin.
5. a kind of new synthetic method of luliconazole key chiral intermediate as described in claim 1, which is characterized in that described
Phase transfer catalyst described in step A is one kind in crown ether-like phase transfer catalysts and quaternary ammonium salt-type phase transfer catalyst.
6. a kind of new synthetic method of luliconazole key chiral intermediate as claimed in claim 5, which is characterized in that described
Crown ether-like phase transfer catalysts are one kind in 15- crown-s 5 and 18- crown-s 6；The quaternary ammonium salt-type phase transfer catalyst is tetraalkyl
One kind in ammonium chloride, tetraalkyl ammonium bromide or tetraalkylammonium iodides.
7. a kind of new synthetic method of luliconazole key chiral intermediate as described in claim 1, which is characterized in that described
Hydrogen source described in step A is one kind in sodium formate, two aqueous sodium bicarbonates, ammonium formate and formic acid/triethylamine.
8. a kind of new synthetic method of luliconazole key chiral intermediate as described in claim 1, which is characterized in that described
Extractant described in step A is one kind in benzene, toluene, ether, hexane and hexamethylene, preferably hexamethylene；In the step B
Extractant is one kind in chloroform, methyl tertiary butyl ether(MTBE), dichloromethane, preferably dichloromethane.
9. a kind of new synthetic method of luliconazole key chiral intermediate as described in claim 1, which is characterized in that described
Drier is at least one of anhydrous sodium sulfate, anhydrous magnesium sulfate, activated carbon and anhydrous calcium chloride.
10. a kind of new synthetic method of luliconazole key chiral intermediate as described in claim 1, which is characterized in that institute
It is one kind in oxalyl chloride, bromine, the halogenated -1- of (R) -2- (2,4- dichlorophenyl) ethyl alcohol and grass to state halogen source object described in step B
The molar ratio of acyl chlorides/bromine is 1: 2~1: 8, preferably 1:3-1：6.
11. a kind of new synthetic method of luliconazole key chiral intermediate as described in claim 1, which is characterized in that institute
State ω-described in step A it is halogenated-molar ratio of 2,4- dichloroacetophenones and chiral catalyst is 50: 1~300: 1, preferably 50: 1
~100: 1；The ω-is halogenated-and 2,4 dichloro benzene ethyl ketone and the molar ratio of surfactant or phase transfer catalyst be 5: 1~30
: 1, preferably 8: 1~15: 1；The ω-is halogenated-and the molar ratio of 2,4- dichloroacetophenones and hydrogen source is 1: 3~1: 20, preferably 1: 5
~1: 10.
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| CN109574797A (en) * | 2018-12-28 | 2019-04-05 | 上海彩迩文生化科技有限公司 | A kind of preparation method of chirality benzylalcohol |
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| CN103044192A (en) * | 2012-12-25 | 2013-04-17 | 爱斯特（成都）医药技术有限公司 | Method for synthesizing luliconazole intermediate-(S)-2,4-dichloro-1-(1,2-dichloroethyl) benzene |
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|---|---|---|---|---|
| CN103044192A (en) * | 2012-12-25 | 2013-04-17 | 爱斯特（成都）医药技术有限公司 | Method for synthesizing luliconazole intermediate-(S)-2,4-dichloro-1-(1,2-dichloroethyl) benzene |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109574797A (en) * | 2018-12-28 | 2019-04-05 | 上海彩迩文生化科技有限公司 | A kind of preparation method of chirality benzylalcohol |
| CN109574797B (en) * | 2018-12-28 | 2021-09-17 | 上海彩迩文生化科技有限公司 | Preparation method of chiral benzyl alcohol |
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