- Evidence for Concert in the Thermal Unimolecular Vinylcyclopropane to Cyclopentene Sigmatropic 1,3-Shift
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Gas phase pyrolysis of cis-2,3-dideuterio-trans-(1'-tert-butyl-2'-(Z)-deuteriovinyl)cyclopropane at 290 deg C gives trans,trans-3,4,5-trideuterio-1-tert-butylcyclopentene as the major 1,3-shift product with greater than 90percent stereospecificity in an orbital symmetry "allowed" suprafacial-inversion sense after correction for the geometric isomerization of starting material and the other materials present.The isotopic substitution at the critical sites of rearrangement eliminates steric of electronic influences of substitutents on a biradical pathway as a source of the suprafacial- inversion stereochemistry observed with more highly substituted drivatives.The stereochemical results coupled with a normal deuterium kinetic isotope effect (kH/2kD=1.14 at 311.6 deg C) at the exo-methylene carbon are best interpreted in terms of a concerted pathway for rearrangement.A less likely alternative is a stereospecific disrotatory ring opening to a biradical followed by rate-determining closure to a five-membered ring.Accompanying the rearrangement is geometric isomerization of starting material resulting from C-1-C-2 bond fission which favors either the single methylene rotation or a double rotation by a factor of 10 over single rotation at the vinyl-bearing carbon.
- Gajewski, Joseph J.,Olson, Leif P.,Willcott, M. Robert
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Read Online
- Safe and environment-friendly preparation method of cyclopropyl acetylene
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The invention relates to the field of medicine synthesis, and discloses a safe and environment-friendly preparation method of cyclopropylacetylene, which comprises the following steps: 1) performing chlorination reaction; 2) carrying out an ethynylation reaction; and 3) synthesizing cyclopropyl methyl ketone from the by-product E/Z-2, 5-dichloro-2-pentene. The process provided by the invention ishigh in chlorination yield; the chlorination reagent is triphosgene, the reaction condition is mild, and the safety is high. An organic solvent, inorganic base and a phase transfer catalyst system areadopted in the ethynylation reaction, and the yield is high; the high-flash-point organic solvent dilutes the reaction system, and the reaction is safe. E/Z-2-5-dichloro-2-pentene generated through the chlorination reaction is subjected to sulfuric acid dechlorination and cyclization and then converted into cyclopropyl methyl ketone, and application is achieved. Potassium chloride is treated as aby-product, and an organic solvent, water, organic alkali and a catalyst are used in chlorination reaction; an organic solvent and a phase transfer catalyst used in the ethynylation reaction can be recycled. The reaction is environment-friendly, only two potassium salt byproducts of potassium chloride and potassium sulfate are formed, and zero emission is basically realized.
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Paragraph 0037-0070
(2020/08/22)
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- Brand-new synthetic process route of cyclopropyl acetylene (by machine translation)
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The process route of, is that the raw materials used by the two-step reaction, are easily available, the reaction conditions are mild, no three wastes are generated, the process route, is easy to operate, the yield is high, the yield is high, the, yield is high, and the industrial production, can be realized through the process route of the process route only through the two-step reaction, scheme of, the process, route shown, in the present invention. (by machine translation)
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Paragraph 0028-0032
(2020/05/30)
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- Palladium-Catalyzed Cascade Intramolecular Cyclization and Allylation of Enynoates with Allylic Alcohols
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A Pd(II)-catalyzed mild and highly regioselective 6-endo cyclization/allylation reaction of enynoates with simple allylic alcohols has been developed. Under mild reaction conditions, the vinyl palladium species generated in situ after cyclization could insert C-C double bond of allylic alcohol through cross-coupling reaction and lead to the formation of allyl pyrone via β-OH elimination. This cascade cross-coupling reaction represents a direct and atom economic methodology for the construction of novel allyl pyrones in moderate to good yields.
- Qiu, Sheng-Qi,Ahmad, Tanveer,Xu, Yun-He,Loh, Teck-Peng
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p. 6729 - 6736
(2019/06/14)
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- METHOD FOR THE MANUFACTURE OF EFAVIRENZ
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This invention relates to a method for the manufacture of optically pure (S)-6- chloro-(cyclopropylethynyl)-1,4-dihydro-4-(trifluoromethyl)-2H-3,1 -benzoxazin- 2-one. Specifically, this invention relates to a flow synthesis method for the manufacture of (S)-6-chloro-(cyclopropylethynyl)-1,4-dihydro-4- (trifluoromethyl)-2H-3,1 -benzoxazin-2-one.
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Page/Page column 23
(2018/09/19)
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- Controlled photorelease of alkynoic acids and their decarboxylative deprotection for copper-catalyzed azide/alkyne cycloaddition
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A controlled photorelease of alkynoic acids from the meso-methyl BODIPY photoremovable protecting group facilitates their subsequent efficient decarboxylation to give terminal alkynes for a CuI-catalyzed azide/alkyne cycloaddition. The quantum efficiencies of the photochemical step and the kinetics of the click reaction step are reported.
- Vohradská, Nikoleta,Sánchez-Carnerero, Esther M.,Pastierik, Tomá?,Mazal, Ctibor,Klán, Petr
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supporting information
p. 5558 - 5561
(2018/06/04)
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- Method for preparing substituted alkynyl group-containing cyclopropyl compound
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The invention relates to the field of organic synthesis, and discloses a method for preparing a substituted alkynyl group-containing cyclopropyl compound. The method comprises the following steps: mixing and reacting a diolefin compound ii used as a starting material with a diazo compound iv in a solvent under the action of a catalyst to obtain a reaction solution containing a propyl compound iii;and adding the obtained reaction solution to acid water or hot water, performing washing, and adding an inorganic or organic alkali to adjust the pH value to 11-14 to prepare the substituted alkynylgroup-containing cyclopropyl compound. The method has the advantages of increase of the yield of the reaction, cheap and readily available industrial raw materials, reduction of by-products and reduction of environmental pollution.
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Paragraph 0026; 0027
(2018/04/03)
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- Preparation method for compound containing alkynyl and cyclopropyl
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The invention relates to the field of organic synthesis, and discloses a preparation method for a compound containing alkynyl and cyclopropyl. The method comprises the following steps: a compound ii with alkyne and alkene is taken as a starting raw material, under effects of a catalyst, the compound ii with the alkyne and the alkene and a diazo substance iv are mixed and reacted in a solvent, andtherefore a reaction liquid containing a compound iii is obtained; and the obtained reaction liquid is added into acid water or hot water for washing, then an inorganic alkali or an organic alkali isadded to adjust the pH to 8-14, and therefore the compound I containing the alkynyl and the cyclopropyl is obtained. The method provided by the invention has the following beneficial effects: 1) the yield of the reaction is improved; 2) the industrialized raw materials used by the method are cheap and easy to obtain; and 3) by-products are reduced, and environmental pollution is reduced.
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Paragraph 0031
(2018/03/07)
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- A method for the preparation of cyclopropyl acetylene (by machine translation)
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The invention discloses a method for the preparation of cyclopropyl acetylene, the preparation method in order to cyclopropane ketone and phosphorus pentachloride as raw materials, in order to waste polyester material in the alcoholysis in the methanol solution of the obtained terephthalic acid armor alcohol ester and glycol as the reaction medium, in - 10 - 0 °C temperature stirring for 1 - 10 hours, then adding potassium hydroxide, stirring at the same temperature the reaction, gas chromatography tracking detection until a reaction is finished, filtering the solid, rectification cyclopropylacetylene product after the purification. In the present invention, waste polyester material in the alcoholysis in the methanol solution of the obtained terephthalic acid armor alcohol ester (DMT) and ethylene glycol (EG) as reaction medium, using a one-pot reaction technology for preparation of cyclopropyl acetylene, such that the process becomes simple, easy to operate, has reduced the three waste discharge, small pollution to the environment, and is a green clean integrated production technology, is suitable for the industrial production of a certain size. The method has not yet been reported, for the preparation of cyclopropyl acetylene provides a new way of thinking. (by machine translation)
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Paragraph 0018; 0019; 0020; 0021; 0022; 0023
(2017/04/29)
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- Preparation method for cyclopropyl acetylene
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The invention relates to a preparation method for cyclopropyl acetylene. The preparation method comprises the following steps: 1) dissolving cyclopropylmethyl ketone, a chlorination reagent, organic base and a catalyst in an organic solvent, carrying out mixing under stirring at 0 to 150 DEG C until reaction is complete and then carrying out distillation and purification to prepare chlorocyclopropylethylene, wherein a mol ratio of cyclopropylmethyl ketone to the chlorination reagent to organic base is 1: (1-5): (1-10); and 2) dissolving chlorocyclopropylethylene and alkali in an organic solvent, carrying out mixing under stirring at 0 to 150 DEG C until reaction is complete and then carrying out distillation and purification to prepare cyclopropyl acetylene, wherein a mol ratio of chlorocyclopropylethylene to alkali is 1: (1-10). According to the preparation method, the organic base, the catalyst and the solvents used in the invention have the characteristics of safety and environment friendliness; reaction conditions are mild, and high temperature and low temperature are not needed; toxic phosgene is not used; the requirement for airtightness of a reaction container is not strict; a reaction solution is cyclically used; treatment of a great amount of phosphorus-containing waste water is not included; and the preparation method has the advantages of high yield (89%), low cost, stability, reliability, safety, environment friendliness, simple operation, suitability for industrial production, etc.
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Paragraph 0049; 0050; 0051; 0052
(2016/12/22)
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- Difluorocyclobutylacetylenes as positive allosteric modulators of mGluR5 with reduced bioactivation potential
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Schizophrenia is a serious illness that affects millions of patients and has been associated with N-methyl-D-aspartate receptor (NMDAR) hypofunction. It has been demonstrated that activation of metabotropic glutamate receptor 5 (mGluR5) enhances NMDA receptor function, suggesting the potential utility of mGluR5 positive allosteric modulators (PAMs) in the treatment of schizophrenia. Herein we describe the optimization of an mGluR5 PAM by replacement of a phenyl with aliphatic heterocycles and carbocycles as a strategy to reduce bioactivation in a biaryl acetylene chemotype. Replacement with a difluorocyclobutane followed by further optimization culminated in the identification of compound 32, a low fold shift PAM with reduced bioactivation potential. Compound 32 demonstrated favorable brain uptake and robust efficacy in mouse novel object recognition (NOR) at low doses.
- Degnan, Andrew P.,Maxwell, Darrell,Balakrishnan, Anand,Brown, Jeffrey M.,Easton, Amy,Gulianello, Michael,Hanumegowda, Umesh,Hill-Drzewi, Melissa,Miller, Regina,Santone, Kenneth S.,Senapati, Arun,Shields, Eric E.,Sivarao, Digavalli V.,Westphal, Ryan,Whiterock, Valerie J.,Zhuo, Xiaoliang,Bronson, Joanne J.,Macor, John E.
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supporting information
p. 5871 - 5876
(2016/12/06)
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- Lanthanide-Catalyzed Reversible Alkynyl Exchange by Carbon–Carbon Single-Bond Cleavage Assisted by a Secondary Amino Group
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Lanthanide-catalyzed alkynyl exchange through C?C single-bond cleavage assisted by a secondary amino group is reported. A lanthanide amido complex is proposed as a key intermediate, which undergoes unprecedented reversible β-alkynyl elimination followed by alkynyl exchange and imine reinsertion. The in situ homo- and cross-dimerization of the liberated alkyne can serve as an additional driving force to shift the metathesis equilibrium to completion. This reaction is formally complementary to conventional alkyne metathesis and allows the selective transformation of internal propargylamines into those bearing different substituents on the alkyne terminus in moderate to excellent yields under operationally simple reaction conditions.
- Shao, Yinlin,Zhang, Fangjun,Zhang, Jie,Zhou, Xigeng
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supporting information
p. 11485 - 11489
(2016/10/24)
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- Aerobic oxynitration of alkynes with tBuONO and TEMPO
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An efficient method for stereoselective nitroaminoxylation of alkyne has been reported. The reaction enjoys a broad substrate scope, good functional group tolerance, and high yields. Synthetically useful α-nitroketones can be accessed through these products in a single step.
- Dutta, Uttam,Maity, Soham,Kancherla, Rajesh,Maiti, Debabrata
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supporting information
p. 6302 - 6305
(2015/02/19)
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- PROCESS FOR THE SYNTHESIS OF ETHYNYLCYCLOPROPANE
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Ethynylcyclopropane is prepared in a two-step process by reacting (1,1-dimethoxyethyl)- cyclopropane with a thiol and eliminating the thiol from the intermediate.
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Page/Page column 7-8
(2009/10/22)
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- Crystalline Efavirenz
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The potent reverse transcriptase inhibitor Efavirenz is produced in crystalline form. Crystalline Efavirenz exists in several physical forms which are-designated Forms 1, 2, 3 and 4, and are characterized by x-ray powder diffraction and differential scanning calorimetry. Pharmaceutical compositions and methods are useful for the treatment of the human immunodeficiency virus (HIV).
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- Preparation of cyclopropylethyne and intermediates for preparation of cyclopropylethyne
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1-chloropropylethyne is prepared by dehydrochlorination with a base of 1-chloro-1-cyclopropylethene, which is itself prepared by treating 1-cyclopropylethanone with dichlorotriarylphosphorane or dichlorotrialkylphosphorane in the presence of a base.
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- Poly(3-cyclopropyl-3-hydroxypropionate) and processes for its preparation and derivatives thereof
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Poly(3-cyclopropyl-3-hydroxypropionates) (I) which are useful for the preparation of vinylcyclopropane and cyclopropylacetylene are disclosed. Methods for the preparation of a variety of intermediates obtained from (I) such as 3-cyclopropyl-3-hydroxypropionic acid and esters and salts thereof, 3-cyclopropylacrylic acid, and vinylcyclopropane also are disclosed.
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- Process for the preparation of cyclopropylacetylene
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The present invention relates generally to novel methods for the preparation of cyclopropylacetylene which is an essential reagent in the asymmetric synthesis of (S)-6-chloro-4-cyclopropylethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one; a useful human immunodeficiency virus (HIV) reverse transcriptase inhibitor with superior anti-retroviral activity. In the process, for example, cyclopropane carboxaldehyde is alkylated to form 1,1,1-trichloro-2-cyclopropyl-ethanol; which in turn undergoes elimination to form 1,1-dichloro-2-cyclopropyl-ethene; which in turn undergoes elimination to form cyclopropyl acetylene.
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Page column 13
(2008/06/13)
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- Process for the preparation of cyclopropylacetylene
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The present invention relates generally to novel methods for the synthesis of cyclopropylacetylene which is an essential reagent in the asymmetric synthesis of (S)-6-chloro-4-cyclopropylethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one; a useful human immunodeficiency virus (HIV) reverse transcriptase inhibitor. In the process, for example, cyclopropane carboxaldehyde is alkylated to form 1,1,1-trichloro-2-cyclopropyl-ethanol; which in turn is hydroxy protected to form 1,1,1-trichloro-2-cyclopropylethyltosylate; which in turn undergoes elimination to form cyclopropyl acetylene. This improvement provides for high conversion of inexpensive, readily available starting materials into cyclopropylacetylene, high overall yields and can be conducted on an industrial scale.
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- Process for the preparation of cyclopropylacetylene
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The present invention relates generally to novel methods for the synthesis of cyclopropylacetylene which is an essential reagent in the asymmetric synthesis of (S)-6-chloro-4-cyclopropylethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one; a useful human immunodeficiency virus (HIV) reverse transcriptase inhibitor.
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- Process for preparing cyclopropylacetylene
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The invention relates to a process for the halogenation of cyclopropylmethyl ketone with at least one dihalo-triorganophosphorane of the general formula I R3PHal2??(I), in which the radicals R can be the same or different and denote a saturated or unsaturated aliphatic C1-C20hydrocarbon radical, a phenyl or (C1-C4alkyl)phenyl radical, which may be optionally substituted by one or two fluorine, chlorine and/or nitro groups, P stands for phosphorus and Hal denotes chlorine, bromine, or iodine, at a temperature of from 800° to 130° C., where the dihalo-triorganophosphane of the general formula (I) is synthesized in situ from triorganophosphane oxide or triorganophosphane sulfide of the general formula II R3PA ??(II), in which R is as defined above with respect to formula I and A denotes oxygen or sulfur, using a halogenating agent, wherein the triorganophosphane oxide or triorganophosphane sulfide is used in catalytic amounts, to the halogenation product of cyclopropylmethyl ketone obtained in said process, and to a process for the conversion of said halogenation product to cyclopropylacetytene.
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- Synthesis of cyclopropylacetylene
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The present invention relates generally to novel methods for the synthesis of cyclopropylacetylene which is a reagent in the asymmetric synthesis of (S)-6-chloro-4-cyclopropylethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one which is a useful human immunodeficiency virus (HIV) reverse transcriptase inhibitor.
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- A new and practical synthesis of vinyl dichlorides via a non-Wittig-type approach
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A practical approach for the conversion of aldehydes to vinyl dichlorides has been developed. These are three-step, one-pot reactions involving the formation of trichlorocarbinol by treatment of aldehydes with trichloroacetic acid and sodium trichloroacetate followed by in situ protection and elimination reactions to form the desired vinyl dichlorides in 85 to 95% yields. (C) 2000 Dupont Pharmaceuticals Company.
- Wang, Zhe,Campagna, Silvio,Xu, Guoyou,Pierce, Michael E.,Fortunak, Joseph M.,Confalone, Pat N.
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p. 4007 - 4009
(2007/10/03)
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- Process for the preparation of cyclopropylacetylene
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The present invention relates generally to novel methods for the synthesis of cyclopropylacetylene which is an essential reagent in the asymmetric synthesis of (S)-6-chloro-4-cyclopropylethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one; a useful human immunodeficiency virus (HIV) reverse transcriptase inhibitor. In the process, cyclopropane carboxaldehyde is condensed with malonic acid to form 3-cyclopropylacrylic acid; 3-cyclopropylacrylic acid is halogenated to form (E,Z)-1-halo-2-cyclopropylethylene; and (E,Z)-1-halo-2-cyclopropylethylene is dehydrohalogenated to form cyclopropyl acetylene. This improvement provides for high conversion of inexpensive, readily available starting materials into cyclopropylacetylene, high overall yields and can be conducted on an industrial scale.
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- Preparation of cycloalkylacetylene compounds using dialkylaminomagnesium halide or bis(dialkylamino)magnesium
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The process of invention reacts an alkynyl halide with a mixture that includes a dialkylaminomagnesium halide or a bis(dialkylamino)magnesium compound to produce a cycloalkylacetylene compound. Preferably, the dialkylaminomagnesium halide compound is of the general formula R 2 NMgX (where R is a linear, branched, or cyclic alkyl substituent or R 2 N represents a heterocyclic alkyl amine and X is Cl, Br, or I) and the bis(dialkylamino)magnesium compound is of the general formula (R 2 N) 2 Mg (where R is a linear, branched, or cyclic alkyl substituent or R 2 N represents a heterocyclic alkylamine). In a preferred method of the invention, the reaction is conducted at moderate temperatures for a period of about 12 to 24 hours. The reaction mixture preferably includes tetrahydrofuran (THF), or a hydrocarbon, or a hydrocarbonether mixture. The preferred compounds produced by this process are cycloalkylacetylene compounds having 5 to 20 carbons, such as cyclopropylacetylene and cyclobutylacetylene.
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- Process for the preparation of cyclopropylacetylene derivatives
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According to the present invention, a process for the preparation of a cyclopropylacetylene derivative represented by the following formula (III): STR1 is provided, which comprises reacting a cyclopropylacrylic acid derivative represented by the following formula (I): STR2 with a halogenating agent to obtain a halogenocyclopropylpropionic acid derivative represented by the following formula (II): STR3 and reacting the halogenocyclopropylpropionic acid derivative with a base.
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- Asymmetric synthesis of benzoxazinones
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The present invention provides novel methods for the asymmetric synthesis of (S)-6-chloro-4-cyclopropylethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one of formula (VI-i) STR1 which is useful as a human immunodeficiency virus (HIV) reverse transcriptase inhibitor.
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- Efficient syntheses of cyclopropylacetylene, a crucial synthetic intermediate for efavirenz (DMP-266)
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Efficient syntheses of cyclopropylacetylene were achieved from cyclopropyl methyl ketone. Different reaction pathways were investigated to avoid the concomitant formation of any side products.
- Schmidt, Shaun E.,Salvatore, Ralph N.,Jung, Kyung Woon,Kwon, Taesoo
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p. 1948 - 1950
(2007/10/03)
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- Practical asymmetric synthesis of Efavirenz (DMP 266), an HIV-1 reverse transcriptase inhibitor
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A highly enantioselective and practical synthesis of the HIV-1 reverse transcriptase inhibitor efavirenz (1) is described. The synthesis proceeds in 62% overall yield in seven steps from 4-chloroaniline (6) to give efavirenz (1) in excellent chemical and optical purity. A novel, enantioselective addition of Li-cyclopropyl acetylide (4a) to p-methoxybenzyl-protected ketoaniline 3a mediated by (1R,2S)-N-pyrrolidinylnorephedrine lithium alkoxide (5a) establishes the stereogenic center in the target with a remarkable level of stereocontrol.
- Pierce, Michael E.,Parsons Jr., Rodney L.,Radesca, Lilian A.,Lo, Young S.,Silverman, Stuart,Moore, James R.,Islam, Qamrul,Choudhury, Anusuya,Fortunak, Joseph M. D.,Nguyen, Dieu,Luo, Chi,Morgan, Susan J.,Davis, Wayne P.,Confalone, Pat N.,Chen, Cheng-Yi,Tillyer, Richard D.,Frey, Lisa,Tan, Lushi,Xu, Feng,Zhao, Dalian,Thompson, Andrew S.,Corley, Edward G.,Grabowski, Edward J. J.,Reamer, Robert,Reider, Paul J.
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p. 8536 - 8543
(2007/10/03)
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- Fibrinogen receptor antagonists
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Fibrinogen receptor antagonists having the structure, for example, of STR1 for example STR2
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- Use of an Ephedrine Alkoxide to Mediate Enantioselective Addition of an Acetylide to a Prochiral Ketone: Asymmetric Synthesis of the Reverse Transcriptase Inhibitor L-743,726.
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The asymmetric synthesis of L-743,726 was achieved in six steps with an overall yield of 31 percent.The asymmetry was introduced using a lithiated ephedrine to mediate acetylide addition to a trifluoromethyl ketone with an enantiomeric excess of 96-98 percent.
- Thompson, Andrew S.,Corley, Edward G.,Huntington, Martha F.,Grabowski, E. J. J.
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p. 8937 - 8940
(2007/10/02)
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