CN104193567B - A kind of simple method for efficiently preparing efavirenz intermediate - Google Patents
A kind of simple method for efficiently preparing efavirenz intermediate Download PDFInfo
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Abstract
The present invention relates to a kind of simple method for efficiently preparing efavirenz intermediate, it belongs to organic compound technical field of catalytic chemistry.This method is using copper as catalyst, using trifluoromethyl ketone and Terminal Acetylenes as raw material, in high yield be prepared for a series of efavirenz intermediates.The characteristics of this method is simple to operate, without any inert gas shielding；Cost is relatively low, without additional any part.Therefore this method will have a wide range of applications in medicine, agricultural chemicals, organic functional material synthesis etc..
Description
Technical field
The present invention relates to a kind of simple method for efficiently preparing efavirenz intermediate, it belongs to organic compound catalysisization
Learn technical field.
Background technology
The addition reaction of trifluoromethyl ketone and Terminal Acetylenes is widely used in the synthesis of medicine, agricultural chemicals and organic functional material,
It is this kind of reaction why it is important the reason for have two：(1) there is an acetylene bond in product, can further carry out functionalization, therefore
It is a kind of important organic synthesis intermediate；(2) while one carbon of carbon is formed, a CF is introduced into target molecule3
Group, this is a potential group with bioactivity and specific physical performance, because artificial synthesized at present
Contain fluorine atom in 30% medicine and 20% agricultural chemicals.Wherein this kind of compound be exactly prepare anti AIDS virus specific drug according to
Fa Weilun important intermediate.
At present, the method for synthesizing efavirenz intermediate in the world has four kinds.As shown in figure 1, first kind method is Germany
Merk companies are raw material with alkynyl lithium reagent and 2,2,2- trifluoroacetophenones, successfully synthesize efavirenz intermediate first
(Organic Synthesis WorkbookII, 2001, Wiley-VCH, 71-84.), this is also current most widely used side
Method (Org.Process Res.Dev., 2003,7,324-328；Angew.Chem.Int.Ed., 2011,50,2957-
2961.).Metal alkine compounds need to be prepared with RMgBr or organolithium reagent, still, these organometallic reagents pair
Water, oxygen sensitive, and synthetic operation is complicated, and produce a large amount of accessory substances.Second class method is with trialkyl silica alkynes and trifluoro
MIBK is raw material, but trialkyl silica alkynes need to just be prepared through two step complexity building-up processes, so as to cause cost it is higher and
Atom economy it is relatively low (Tetrahedron Lett., 2006,47,8083-8086；J.Org.Chem., 2011,76,4482-
4488.).3rd class method is to prepare efavirenz intermediate by the trifluoromethylation reaction of alkynyl ketone, and this method needs
Trifluoromethyl reagent Me3SiCF3Or HCF3, the preparation of this kind of reagent can use the BrCF to damage the ozone layer3, and HCF3Itself
Be exactly a kind of greenhouse gases (Org.Lett., 2010,12,5104-5107；Eur.J.Org.Chem., 2011,5959-5961；
Org.Biomol.Chem., 2013,11,1446-1450.).
In order to solve the deficiency of above-mentioned three kinds of methods, Japanese Scientists Shibasaki in 2007 etc. reports trifluoro first
The method that the direct alkynyl of MIBK prepares efavirenz intermediate, the method need copper to make catalyst, and Phosphine ligands and diamines are made
For part (Org.Lett., 2007,9,2997-3000.).Shibasaki discovery causes the extensive pass of chemist
Note, a series of recent Ag/PCy3, CuI/ Cabbeens, Ti/ quinines and silver nanoparticle heterogeneous catalysis be successfully applied to fluoroform
Base ketone alkynylation reaction (Synlett, 2008,1571-1573；Adv.Synth.Catal., 2013,355,3517-3521；
Angew.Chem.Int.Ed., 2011,50,3538-3542；ChemCatChem, 2014,6,580-591.).Trifluoromethyl ketone
Direct alkynylation reaction embody the principle of Atom economy really, there is higher academic significance and application background.But this
The factor for limiting its commercial Application also be present in kind method, such as：Need part costly, to water or oxygen sensitive.Therefore,
We have developed a kind of simple efficient method that efavirenz intermediate is prepared without any additional part.
The content of the invention
The purpose of the present invention is to have invented a kind of simple method for efficiently preparing efavirenz intermediate, it is intended to for Wei in accordance with the law
The preparation of logical sequence intermediate provide it is a kind of it is simple, efficiently, be easy to industrialized method.
The technical scheme is that：A kind of simple method for efficiently preparing efavirenz intermediate, it is characterised in that：It is first
It is first successively that trifluoromethyl ketone (0.5mmol), Terminal Acetylenes (1.0mmol), copper (10mol%), alkali (20mol%) and 1mL is organic molten
Agent, which adds, is permitted in woods gram bottle, the stirring reaction 24h at 50 DEG C, after reaction terminates, adds 15mL saturated aqueous common salts and reaction is quenched, instead
Mixture dichloromethane (15mL × 3) extractive reaction product is answered, merges organic phase, organic solvent is removed in the case where rotating instrument, is used
Column chromatography for separation, obtain analytically pure efavirenz intermediate.
In above-mentioned preparation method, the copper is selected from CuI, CuCl, Cu2O、CuOH、Cu、CuO、CuSO4、Cu(NO3)2、Cu
(OH)2、Cu(CH3COO)2。
In above-mentioned preparation method, the alkali is selected from K2CO3、K3PO4·3H2O、KOH、NaOH、Na2CO3、NaHCO3、
Cs2CO3、KOtBu、NaOtBu。
In above-mentioned preparation method, the organic solvent is selected from tetrahydrofuran (THF), toluene, DMF
(DMF), DMA (DMA), 1-METHYLPYRROLIDONE (NMP), ethanol, isopropanol, ethylene glycol.
In above-mentioned preparation method, the trifluoromethyl ketone be selected from 2,2,2- trifluoroacetophenones, 1- (4 '-chlorphenyl) -2,2,
2- trifluoroethanones, 1- (4 '-bromophenyl) -2,2,2- trifluoroethanones, 1- (4 '-tolyl) -2,2,2- trifluoroethanones, 3,3,3- tri-
Fluoropyruvate ethyl ester, 1- (2 '-amino -5 '-chlorphenyl) -2,2,2- trifluoroethanones.
In above-mentioned preparation method, the terminal alkyne compound be selected from phenylacetylene, 4- methyl phenylacetylene, 4- Methoxy-phenylacetylenes,
4- phenyl ethynyl phenyls, 4- bromobenzenes acetylene, 4- fluorobenzene acetylene, 4- chlorobenzenes acetylene, 3- methyl phenylacetylene, 3- fluorobenzene acetylene, cyclopropyl
Acetylene, cyclohexyl-acetylene, cyclohexenyl group acetylene, heptyne, 3- thiophene acetylenes.
The beneficial effects of the invention are as follows：A kind of simple method for efficiently preparing efavirenz intermediate is developed first.Should
Method will have a wide range of applications in medicine, agricultural chemicals, organic functional material synthesis etc..
Brief description of the drawings
Accompanying drawing 1 is four kinds of synthetic methods of efavirenz intermediate
Embodiment
Specific embodiment 1
Successively by 2,2,2- trifluoroacetophenones (0.5mmol), phenylacetylene (1.0mmol), CuI (0.05mmol), K2CO3
(0.1mmol) and THF (1mL) are added in woods gram bottle perhaps, the stirring reaction 24h under the conditions of 50 DEG C, thin-layer chromatography tracking reaction.
After reaction terminates, add 15mL saturated aqueous common salts and reaction is quenched, reactant mixture is produced with dichloromethane (15mL × 3) extractive reaction
Thing, merge organic phase, be concentrated to give crude product using Rotary Evaporators, column chromatography obtains target product, the eluent of column chromatography
It is petroleum ether: ethyl acetate (10: 1), product structure are identified by NMR and high resolution mass spectrum.Separation yield is up to 99%.
Specific embodiment 2
Successively by 2,2,2- trifluoroacetophenones (0.5mmol), 4- methyl phenylacetylene (1.0mmol), CuCl (0.05mmol),
Na2CO3(0.1mmol) and DMF (1mL) are added in woods gram bottle perhaps, the stirring reaction 24h under the conditions of 50 DEG C, thin-layer chromatography tracking
Reaction.After reaction terminates, add 15mL saturated aqueous common salts and reaction is quenched, reactant mixture is extracted with dichloromethane (15mL × 3)
Reaction product, merge organic phase, be concentrated to give crude product using Rotary Evaporators, column chromatography obtains target product, column chromatography
Eluent is petroleum ether: ethyl acetate (10: 1), and product structure is identified by NMR and high resolution mass spectrum.Separation yield is up to 94%.
Specific embodiment 3
Successively by 2,2,2- trifluoroacetophenones (0.5mmol), 4- Methoxy-phenylacetylenes (1.0mmol), Cu (0.05mmol),
NaHCO3(0.1mmol) and toluene (1mL) are added in woods gram bottle perhaps, the stirring reaction 24h under the conditions of 50 DEG C, thin-layer chromatography with
Track reacts.After reaction terminates, add 15mL saturated aqueous common salts and reaction is quenched, reactant mixture is extracted with dichloromethane (15mL × 3)
Reaction product is taken, merges organic phase, is concentrated to give crude product using Rotary Evaporators, column chromatography obtains target product, and column chromatography is used
Eluent be petroleum ether: ethyl acetate (10: 1), product structure, which passes through NMR and high resolution mass spectrum, to be identified.Separation yield reaches
95%.
Specific embodiment 4
Successively by 2,2,2- trifluoroacetophenones (0.5mmol), 4- Liquid Crystal Compounds Intermediate p-Ethyl-phenylacetylenes (1.0mmol), Cu2O(0.05mmol)、
K3PO4·3H2O (0.1mmol) and NMP (1mL) are added in woods gram bottle perhaps, the stirring reaction 24h under the conditions of 50 DEG C, thin layer color
Spectrum tracking reaction.After reaction terminates, add 15mL saturated aqueous common salts and be quenched reaction, reactant mixture with dichloromethane (15mL ×
3) extractive reaction product, merge organic phase, be concentrated to give crude product using Rotary Evaporators, column chromatography obtains target product, post layer
The eluent of analysis is petroleum ether: ethyl acetate (10: 1), and product structure is identified by NMR and high resolution mass spectrum.Separation yield
Up to 97%.
Specific embodiment 5
Successively by 2,2,2- trifluoroacetophenones (0.5mmol), 4- phenyl ethynyl phenyls (1.0mmol), CuO (0.05mmol),
NaOH (0.1mmol) and DMA (1mL) are added in woods gram bottle perhaps, the stirring reaction 24h under the conditions of 50 DEG C, thin-layer chromatography tracking
Reaction.After reaction terminates, add 15mL saturated aqueous common salts and reaction is quenched, reactant mixture is extracted with dichloromethane (15mL × 3)
Reaction product, merge organic phase, be concentrated to give crude product using Rotary Evaporators, column chromatography obtains target product, column chromatography
Eluent is petroleum ether: ethyl acetate (10: 1), and product structure is identified by NMR and high resolution mass spectrum.Separation yield is up to 94%.
Specific embodiment 6
Successively by 2,2,2- trifluoroacetophenones (0.5mmol), 4- fluorobenzene acetylene (1.0mmol), Cu (NO3)2
(0.05mmol), KOH (0.1mmol) and DMF (1mL) are added in woods gram bottle perhaps, and stirring reaction 24h, thin under the conditions of 50 DEG C
Layer chromatography tracking reaction.After reaction terminates, add 15mL saturated aqueous common salts and reaction, reactant mixture dichloromethane is quenched
(15mL × 3) extractive reaction product, merge organic phase, be concentrated to give crude product using Rotary Evaporators, column chromatography obtains target production
Thing, the eluent of column chromatography is petroleum ether: ethyl acetate (10: 1), and product structure is identified by NMR and high resolution mass spectrum.Point
From yield up to 91%.
Specific embodiment 7
Successively by 2,2,2- trifluoroacetophenones (0.5mmol), 4- chlorobenzenes acetylene (1.0mmol), CuSO4(0.05mmol)、
Cs2CO3(0.1mmol) and ethanol (1mL) are added in woods gram bottle perhaps, the stirring reaction 24h under the conditions of 50 DEG C, thin-layer chromatography with
Track reacts.After reaction terminates, add 15mL saturated aqueous common salts and reaction is quenched, reactant mixture is extracted with dichloromethane (15mL × 3)
Reaction product is taken, merges organic phase, is concentrated to give crude product using Rotary Evaporators, column chromatography obtains target product, and column chromatography is used
Eluent be petroleum ether: ethyl acetate (10: 1), product structure, which passes through NMR and high resolution mass spectrum, to be identified.Separation yield reaches
69%.
Specific embodiment 8
Successively by 2,2,2- trifluoroacetophenones (0.5mmol), 4- bromobenzenes acetylene (1.0mmol), Cu (CH3COO)2
(0.05mmol)、K2CO3(0.1mmol) and isopropanol (1mL) are added in woods gram bottle perhaps, the stirring reaction under the conditions of 50 DEG C
24h, thin-layer chromatography tracking reaction.After reaction terminates, add 15mL saturated aqueous common salts and reaction, reactant mixture dichloromethane is quenched
Alkane (15mL × 3) extractive reaction product, merge organic phase, be concentrated to give crude product using Rotary Evaporators, column chromatography obtains target
Product, the eluent of column chromatography is petroleum ether: ethyl acetate (10: 1), and product structure is identified by NMR and high resolution mass spectrum.
Separation yield is up to 71%.
Specific embodiment 9
Successively by 2,2,2- trifluoroacetophenones (0.5mmol), 3- fluorobenzene acetylene (1.0mmol), CuOH (0.05mmol),
K2CO3(0.1mmol) and DMA (1mL) are added in woods gram bottle perhaps, the stirring reaction 24h under the conditions of 50 DEG C, thin-layer chromatography tracking
Reaction.After reaction terminates, add 15mL saturated aqueous common salts and reaction is quenched, reactant mixture is extracted with dichloromethane (15mL × 3)
Reaction product, merge organic phase, be concentrated to give crude product using Rotary Evaporators, column chromatography obtains target product, column chromatography
Eluent is petroleum ether: ethyl acetate (10: 1), and product structure is identified by NMR and high resolution mass spectrum.Separation yield is up to 68%.
Specific embodiment 10
Successively by 2,2,2- trifluoroacetophenones (0.5mmol), 3- methyl phenylacetylene (1.0mmol), Cu2O(0.05mmol)、
K2CO3(0.1mmol) and NMP (1mL) are added in woods gram bottle perhaps, the stirring reaction 24h under the conditions of 50 DEG C, thin-layer chromatography tracking
Reaction.After reaction terminates, add 15mL saturated aqueous common salts and reaction is quenched, reactant mixture is extracted with dichloromethane (15mL × 3)
Reaction product, merge organic phase, be concentrated to give crude product using Rotary Evaporators, column chromatography obtains target product, column chromatography
Eluent is petroleum ether: ethyl acetate (10: 1), and product structure is identified by NMR and high resolution mass spectrum.Separation yield is up to 68%.
Specific embodiment 11
Successively by 2,2,2- trifluoroacetophenones (0.5mmol), cyclopropyl acethlene (1.0mmol), CuI (0.05mmol), KOH
(0.1mmol) and THF (1mL) are added in woods gram bottle perhaps, the stirring reaction 24h under the conditions of 50 DEG C, thin-layer chromatography tracking reaction.
After reaction terminates, add 15mL saturated aqueous common salts and reaction is quenched, reactant mixture is produced with dichloromethane (15mL × 3) extractive reaction
Thing, merge organic phase, be concentrated to give crude product using Rotary Evaporators, column chromatography obtains target product, the eluent of column chromatography
It is petroleum ether: ethyl acetate (10: 1), product structure are identified by NMR and high resolution mass spectrum.Separation yield is up to 72%.
Specific embodiment 12
Successively by 2,2,2- trifluoroacetophenones (0.5mmol), cyclohexyl-acetylene (1.0mmol), CuCl (0.05mmol),
KOH (0.1mmol) and THF (1mL) are added in woods gram bottle perhaps, the stirring reaction 24h under the conditions of 50 DEG C, and thin-layer chromatography tracking is anti-
Should.After reaction terminates, add 15mL saturated aqueous common salts and reaction is quenched, reactant mixture is extracted anti-with dichloromethane (15mL × 3)
Product is answered, merges organic phase, is concentrated to give crude product using Rotary Evaporators, column chromatography obtains target product, and column chromatography is washed
De- liquid is petroleum ether: ethyl acetate (10: 1), and product structure is identified by NMR and high resolution mass spectrum.Separation yield is up to 51%.
Specific embodiment 13
Successively by 2,2,2- trifluoroacetophenones (0.5mmol), cyclohexenyl group acetylene (1.0mmol), Cu (CH3COO)2
(0.05mmol), NaOH (0.1mmol) and DMF (1mL) are added in woods gram bottle perhaps, and stirring reaction 24h, thin under the conditions of 50 DEG C
Layer chromatography tracking reaction.After reaction terminates, add 15mL saturated aqueous common salts and reaction, reactant mixture dichloromethane is quenched
(15mL × 3) extractive reaction product, merge organic phase, be concentrated to give crude product using Rotary Evaporators, column chromatography obtains target production
Thing, the eluent of column chromatography is petroleum ether: ethyl acetate (10: 1), and product structure is identified by NMR and high resolution mass spectrum.Point
From yield up to 68%.
Specific embodiment 14
Successively by 2,2,2- trifluoroacetophenones (0.5mmol), heptyne (1.0mmol), CuO (0.05mmol), NaOH
(0.1mmol) and DMA (1mL) are added in woods gram bottle perhaps, the stirring reaction 24h under the conditions of 50 DEG C, thin-layer chromatography tracking reaction.
After reaction terminates, add 15mL saturated aqueous common salts and reaction is quenched, reactant mixture is produced with dichloromethane (15mL × 3) extractive reaction
Thing, merge organic phase, be concentrated to give crude product using Rotary Evaporators, column chromatography obtains target product, the eluent of column chromatography
It is petroleum ether: ethyl acetate (10: 1), product structure are identified by NMR and high resolution mass spectrum.Separation yield is up to 31%.
Specific embodiment 15
Successively by 2,2,2- trifluoroacetophenones (0.5mmol), 3- thiophene acetylenes (1.0mmol), CuO (0.05mmol),
NaOH (0.1mmol) and toluene (1mL) are added in woods gram bottle perhaps, the stirring reaction 24h under the conditions of 50 DEG C, thin-layer chromatography tracking
Reaction.After reaction terminates, add 15mL saturated aqueous common salts and reaction is quenched, reactant mixture is extracted with dichloromethane (15mL × 3)
Reaction product, merge organic phase, be concentrated to give crude product using Rotary Evaporators, column chromatography obtains target product, column chromatography
Eluent is petroleum ether: ethyl acetate (10: 1), and product structure is identified by NMR and high resolution mass spectrum.Separation yield is up to 90%.
Specific embodiment 16
Successively by 1- (4 '-chlorphenyl) -2,2,2- trifluoroethanones (0.5mmol), cyclopropyl acethlene (1.0mmol), CuI
(0.05mmol), KOH (0.1mmol) and ethanol (1mL) are added in woods gram bottle perhaps, and stirring reaction 24h, thin under the conditions of 50 DEG C
Layer chromatography tracking reaction.After reaction terminates, add 15mL saturated aqueous common salts and reaction, reactant mixture dichloromethane is quenched
(15mL × 3) extractive reaction product, merge organic phase, be concentrated to give crude product using Rotary Evaporators, column chromatography obtains target production
Thing, the eluent of column chromatography is petroleum ether: ethyl acetate (10: 1), and product structure is identified by NMR and high resolution mass spectrum.Point
From yield up to 78%.
Specific embodiment 17
Successively by 1- (4 '-bromophenyl) -2,2,2- trifluoroethanones (0.5mmol), phenylacetylene (1.0mmol), CuI
(0.05mmol), NaOH (0.1mmol) and ethanol (1mL) are added in woods gram bottle perhaps, the stirring reaction 24h under the conditions of 50 DEG C,
Thin-layer chromatography tracking reaction.After reaction terminates, add 15mL saturated aqueous common salts and reaction, reactant mixture dichloromethane is quenched
(15mL × 3) extractive reaction product, merge organic phase, be concentrated to give crude product using Rotary Evaporators, column chromatography obtains target production
Thing, the eluent of column chromatography is petroleum ether: ethyl acetate (10: 1), and product structure is identified by NMR and high resolution mass spectrum.Point
From yield up to 97%.
Specific embodiment 18
Successively by 1- (4 '-tolyl) -2,2,2- trifluoroethanones (0.5mmol), phenylacetylene (1.0mmol), CuI
(0.05mmol), NaOtBu (0.1mmol) and isopropanol (1mL) are added in woods gram bottle perhaps, the stirring reaction under the conditions of 50 DEG C
24h, thin-layer chromatography tracking reaction.After reaction terminates, add 15mL saturated aqueous common salts and reaction, reactant mixture dichloromethane is quenched
Alkane (15mL × 3) extractive reaction product, merge organic phase, be concentrated to give crude product using Rotary Evaporators, column chromatography obtains target
Product, the eluent of column chromatography is petroleum ether: ethyl acetate (10: 1), and product structure is identified by NMR and high resolution mass spectrum.
Separation yield is up to 77%.
Specific embodiment 19
Successively by 3,3,3- trifluoroacetone acetoacetic esters (0.5mmol), phenylacetylene (1.0mmol), CuI (0.05mmol),
KOtBu (0.1mmol) and ethanol (1mL) are added in woods gram bottle perhaps, the stirring reaction 24h under the conditions of 50 DEG C, thin-layer chromatography with
Track reacts.After reaction terminates, add 15mL saturated aqueous common salts and reaction is quenched, reactant mixture is extracted with dichloromethane (15mL × 3)
Reaction product is taken, merges organic phase, is concentrated to give crude product using Rotary Evaporators, column chromatography obtains target product, and column chromatography is used
Eluent be petroleum ether: ethyl acetate (10: 1), product structure, which passes through NMR and high resolution mass spectrum, to be identified.Separation yield reaches
98%.
Specific embodiment 20
Successively by 1- (2 '-amino -5 '-chlorphenyl) -2,2,2- trifluoroethanones (0.5mmol), phenylacetylene (1.0mmol),
CuI(0.05mmol)、K2CO3(0.1mmol) and DMF (1mL) are added in woods gram bottle perhaps, the stirring reaction under the conditions of 50 DEG C
24h, thin-layer chromatography tracking reaction.After reaction terminates, add 15mL saturated aqueous common salts and reaction, reactant mixture dichloromethane is quenched
Alkane (15mL × 3) extractive reaction product, merge organic phase, be concentrated to give crude product using Rotary Evaporators, column chromatography obtains target
Product, the eluent of column chromatography is petroleum ether: ethyl acetate (10: 1), and product structure is identified by NMR and high resolution mass spectrum.
Separation yield is up to 85%.
Claims (4)
- A kind of 1. simple method for efficiently preparing efavirenz intermediate, it is characterised in that：First successively by 0.5mmol trifluoro The Terminal Acetylenes of MIBK, 1.0mmol, in terms of trifluoromethyl ketone, 10mol% copper catalyst, 20mol% alkali and 1mL are organic molten Agent, which adds, is permitted in woods gram bottle, the stirring reaction 24h at 50 DEG C, after reaction terminates, adds 15mL saturated aqueous common salts and reaction is quenched, instead The dichloromethane extractive reaction product of mixture 15mL × 3 is answered, merges organic phase, organic solvent is removed in the case where rotating instrument, is used Column chromatography for separation, obtain analytically pure efavirenz intermediate；The trifluoromethyl ketone is selected from 2,2,2- trifluoroacetophenones, and end-group alkyne is phenylacetylene, 4- methyl phenylacetylene, 4- methoxybenzenes Acetylene, 4- Liquid Crystal Compounds Intermediate p-Ethyl-phenylacetylenes, 4- phenyl ethynyl phenyls or 3- thiophene acetylenes；Or trifluoromethyl ketone is 1- (4 '-bromophenyl) -2, 2,2- trifluoroethanones, end-group alkyne are phenylacetylene；Or trifluoromethyl ketone is 3,3,3- trifluoroacetone acetoacetic esters, Terminal Acetylenes is benzene second Alkynes.
- A kind of 2. simple method for efficiently preparing efavirenz intermediate according to claim 1, it is characterised in that：It is described Copper catalyst is selected from CuI, CuCl, Cu2O、CuOH、Cu、CuO、CuSO4、Cu(NO3)2、Cu(OH)2、Cu(CH3COO)2。
- A kind of 3. simple method for efficiently preparing efavirenz intermediate according to claim 1, it is characterised in that：It is described Alkali is selected from K2CO3、K3PO4·3H2O、KOH、NaOH、Na2CO3、NaHCO3、Cs2CO3、KOtBu、NaOtBu。
- A kind of 4. simple method for efficiently preparing efavirenz intermediate according to claim 1, it is characterised in that：It is described Organic solvent is selected from tetrahydrofuran, toluene, DMF, DMA, 1-METHYLPYRROLIDONE, second Alcohol, isopropanol, ethylene glycol.
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| 《Copper(I) Alkoxide-Catalyzed Alkynylation of Trifluoromethyl Ketones》;Rie Motoki et al.;《Org.Lett.》;20070713;第9卷(第16期);2997-3000 * |
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| CN104193567A (en) | 2014-12-10 |
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