- Formation of fulvene and dimethylenecyclopentenyl titanium complexes from bis(η5-tetramethylcyclopentadienyl)titanium(IV) precursors
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A mixture of isomeric (Me4C5H)(Me3C5(CH2)H)TiMe compounds was obtained by thermally induced methane elimination from (Me4C5H)2TiMe2 at 130 deg C, analogous to the formation of (Me5C5)(Me4C5(CH2))TiMe.The compound (Me5C5)(Me3C5(CH2)2)Ti was newly prepared in 27percent yield by boiling a (Me5C5)2TiCl2-LiAlH4 mixture in toluene, followed by sublimation of the soluble product.By an analogous process, (Me4C5H)(Me2C5(CH2)2H)Ti was obtained in 10percent yield.Neither type of complex was formed by either method from titanocene derivatives with fewer methyl groups at cyclopentadienyl ligands.
- Mach, Karel,Varga, Vojtech,Hanus, Vladimir,Sedmera, Petr
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- Total Synthesis of Bis-anthraquinone Antibiotic BE-43472B
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This is a full account of our synthetic endeavor on the total synthesis of bis-anthraquinone antibiotic BE-43472B, an unusual octacyclic aromatic polyketide with a bis-anthraquinone scaffold. Three key steps enabled a facile access to the anthraquinone unit corresponding to the ABCF rings; (1) cyclo-condensation or -addition of benzonitrile oxides with cyclic enone derivatives, (2) benzoin cyclization for the stereoselective ring fusion with an angular hydroxy group, and (3) pinacol rearrangement for stereoselective installation of the angular aryl group. Other keys for the success include, (4) diastereoselective methylation of a lactol derivative, and (5) late-stage installation of the C3 hydroxy group through stereoselective oxirane ring formation via halohydrin derivatives. Whereas oxidation of the double bond in the enone with an adjacent 1,3-diketone moiety failed, the projected oxidation was achieved with the alkene keeping the isoxazole moiety intact as a 1,3-diketone equivalent. In the racemic total synthesis, X-ray crystal structure analysis of the target was achieved, proving the three-dimensional architecture for the first time. The asymmetric total synthesis was also achieved by exploiting a cycloadduct of the nitrile oxide and the enantiomerically pure cyclohexenone, which was convertible to the common intermediate via dehydrogenation followed by alkoxycarbonylation.
- Yamashita, Yu,Hirano, Yoichi,Takada, Akiomi,Takikawa, Hiroshi,Suzuki, Keisuke
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- 1H and 13C NMR spectroscopic study of titanium(IV) species formed by activation of Cp2TiCl2 and [(Me4C5)SiMe2NtBu]TiCl2 with methylaluminoxane (MAO)
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Using 13C and 1H NMR spectroscopy, the products of the reaction of Cp2TiCl2 with methylaluminoxane (MAO) at Al:Ti ratios of 5:1 to 300:1 have been identified as Cp2TiMeCl, Cp2TiMe2, [Cp2TiMe(μ-Cl)Cp2-TiCl]+[Me-MAO]- (II1), [Cp2TiMe(μ-Cl)Cp2TiMe]+[Me-MAO]- (II2), [Cp2TiMe(μ-Me)Cp2TiMe]+[Me-MAO]- (II3), the heterobinuclear ion pair [Cp2Ti(μ-Me)2AlMe2]+[Me-MAO] - (III), and a zwitterion-like intermediate, formulated as Cp2TiMe+←Me-Al-≡MAO (IV). In contrast, [(Me4C5)SiMe2NtBu]TiCl2/M AO gives only zwitterion-like, not heterobinuclear, species.
- Bryliakov, Konstantin P.,Talsi, Evgenii P.,Bochmann, Manfred
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- Azulichlorins and Benzocarbachlorins Derived Therefrom
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Acid-catalyzed condensation of azulidipyrrane aldehydes with a dihydrodipyrrin carbaldehyde afforded the first examples of azulichlorins. These macrocyclic products were isolated in a monoprotonated form, and the free bases proved to be somewhat unstable. The monocations were strongly diatropic, and proton NMR spectroscopy showed the internal C-H at ca. -2 ppm. Addition of TFA gave the related dications, but these exhibited significantly reduced aromatic ring currents. Reaction of an azulichlorin with tert-butyl hydroperoxide and KOH in dichloromethane/methanol gave a benzocarbachlorin and two related aldehydes. The UV-vis spectrum for the benzocarbachlorin showed a split Soret band at 414 and 430 nm, together with a strong chlorin-like absorption at 684 nm. The proton NMR spectrum indicated that the carbachlorin is strongly aromatic and the internal C-H was observed at -4.64 ppm. Addition of TFA afforded a C-protonated dication with a significantly increased diatropic ring current. The proton NMR spectrum, NICS calculations, and AICD plots indicated that the system favors a 22πelectron delocalization pathway that runs through the fused benzo unit. Addition of TFA to the benzocarbachlorin aldehydes primarily led to the formation of monocations, and the generation of C-protonated dications was no longer favored due to the presence of electron-withdrawing formyl moieties.
- Noboa, Mario A.,Abusalim, Deyaa I.,Lash, Timothy D.
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- A practical and inexpensive one-pot synthesis of bis(indenyl) dimethyltitanium with aqueous workup procedure
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A simple, reliable, and reproducible procedure for the multi-gram synthesis of highly pure bis(indenyl)dimethyltitanium is presented. The procedure relies on a one-pot conversion of inexpensive indene, methyllithium, and titanium tetrachloride to [Ind2TiMe2] and a convenient and quick aqueous workup protocol. Overall, quantities of several grams of [Ind 2TiMe2] can be synthesized within a few hours. The procedure can also be used for the synthesis of [Cp2TiMe2] from cyclopentadiene, methyllithium, and titanium tetrachloride.
- Ross, Jan H.,Preuss, Till,Brahms, Christian,Doye, Sven
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- Preparation of (+)-nemorensic acid and approaches to nemorensine using the partial reduction of electron deficient furans
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Starting from a commercially available furoic acid, the synthesis of (+)-nemorensic acid is described in nine steps, and in 32% overall yield. Key steps in our sequence are a chiral auxiliary controlled, stereoselective, Birch reduction of 3-methyl-2-furo
- Donohoe, Timothy J.,Guillermin, Jean-Baptiste,Walter, Daryl S.
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- New molecular design for blue BODIPYs
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Diverse dihydrodipyrrins are available as precursors in the de novo synthesis of bacteriochlorins and chlorins. Each dihydrodipyrrin contains one pyrrole and one pyrroline (3,4-dihydropyrrole) ring joined at the respective α-positions via a methylene unit as well as a geminal-dimethyl group at one of the pyrroline β-positions. Complexation of the dihydrodipyrrin ligands occurs smoothly upon treatment with Bu2B-OTf or BF3·OEt2 in dichloromethane containing triethylamine at room temperature. Six such dihydrodipyrrinatoboron complexes have been prepared and are examined here. The complexes with -BF2 or -BBu2 absorb in the blue region (λabs ~ 400 nm) and fluoresce (λem ~ 500 nm) with large Stokes shift (~100-150 nm), almost no absorption-fluorescence spectral overlap, and high fluorescence quantum yield (Φf ~ 0.4-0.9). The spectral features are rather insensitive to substituents in the pyrrole nucleus (carboethoxy, bromo, and p-tolyl) and the presence of a 1-naphthalenyl group at the meso-position. In one case examined, the spectral properties including Φf value were almost identical in toluene and acetonitrile. The blue BODIPYs may be useful as broadband photosensitizers upon violet-laser excitation.
- Wu, Zhiyuan,Fujita, Hikaru,Magdaong, Nikki Cecil M.,Diers, James R.,Hood, Don,Allu, Srinivasarao,Niedzwiedzki, Dariusz M.,Kirmaier, Christine,Bocian, David F.,Holten, Dewey,Lindsey, Jonathan S.
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- ATTRACTANT COMPOSITION FOR THE SPECIES DELOTTOCOCCUS ABERIAE, METHODS FOR THE MONITORING, DETECTION AND/OR CONTROL OF THE PEST
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The present invention relates to the compound (4,5,5-trimethyl-3-methylenecyclopent-1-en-1-yl)methyl acetate and to an attractant composition for insects of the species Delottococcus aberiae comprising said compound. The present invention also relates to an attractant device for Delottococcus aberiae comprising said compound or said composition, and to a method for the control and/or monitoring of the populations of insects of the species Delottococcus aberiae.
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Paragraph 0045; 0048
(2022/01/12)
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- Oxidation Under Reductive Conditions: From Benzylic Ethers to Acetals with Perfect Atom-Economy by Titanocene(III) Catalysis
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Described here is a titanocene-catalyzed reaction for the synthesis of acetals and hemiaminals from benzylic ethers and benzylic amines, respectively, with pendant epoxides. The reaction proceeds by catalysis in single-electron steps. The oxidative addition comprises an epoxide opening. An H-atom transfer, to generate a benzylic radical, serves as a radical translocation step, and an organometallic oxygen rebound as a reductive elimination. The reaction mechanism was studied by high-level dispersion corrected hybrid functional DFT with implicit solvation. The low-energy conformational space was searched by the efficient CREST program. The stereoselectivity was deduced from the lowest lying benzylic radical structures and their conformations are controlled by hyperconjugative interactions and steric interactions between the titanocene catalyst and the aryl groups of the substrate. An interesting mechanistic aspect is that the oxidation of the benzylic center occurs under reducing conditions.
- Funk, Pierre,Richrath, Ruben B.,Bohle, Fabian,Grimme, Stefan,Gans?uer, Andreas
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supporting information
p. 5482 - 5488
(2021/02/03)
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- Reductive C-O, C-N, and C-S Cleavage by a Zirconium Catalyzed Hydrometalation/β-Elimination Approach
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A zirconium catalyzed reductive cleavage of Csp3 and Csp2 carbon-heteroatom bonds is reported that makes use of a tethered alkene functionality as a traceless directing group. The reaction is successfully demonstrated on C-O, C-N, and C-S bonds and proposed to proceed via a hydrozirconation/β-heteroatom elimination sequence of an in situ formed zirconium hydride catalyst. The positional isomerization of the catalyst further enables the cleavage of homoallylic ethers and the removal of terminal allyl and propargyl groups.
- Matt, Christof,K?lblin, Frederic,Streuff, Jan
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supporting information
p. 6983 - 6988
(2019/09/09)
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- Annulated bacteriochlorins for near-infrared photophysical studies
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Molecules with strong absorption in the near-infrared (NIR) spectral region are of interest for a variety of applications in the photosciences. Nature's NIR absorbers are bacteriochlorophylls, which contain a tetrahydroporphyrin chromophore accentuated by
- Fujita, Hikaru,Jing, Haoyu,Krayer, Michael,Allu, Srinivasarao,Veeraraghavaiah, Gorre,Wu, Zhiyuan,Jiang, Jianbing,Diers, James R.,Magdaong, Nikki Cecil M.,Mandal, Amit K.,Roy, Arpita,Niedzwiedzki, Dariusz M.,Kirmaier, Christine,Bocian, David F.,Holten, Dewey,Lindsey, Jonathan S.
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p. 7209 - 7232
(2019/05/24)
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- Access to Enantiopure Advanced Intermediates en Route to Madangamines
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The synthesis of enantiopure ABCE and ABCD tetracyclic advanced intermediates en route to madangamine alkaloids and studies for the construction of the triunsaturated 15-membered D ring of madangamine B and the saturated 13-membered D ring of madangamine E are reported.
- Are, Celeste,Pérez, Maria,Ballette, Roberto,Proto, Stefano,Caso, Federica,Yayik, Nihan,Bosch, Joan,Amat, Mercedes
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supporting information
p. 15929 - 15933
(2019/11/22)
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- Highly (Z)-Diastereoselective Synthesis of Trifluoromethylated exo-Glycals via Photoredox and Copper Catalysis
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Highly (Z)-diastereoselective approaches for the synthesis of trifluoromethylated exo-glycals by copper and photoredox catalysis are described. These complementary reactions are applicable to a wide range of methylene exo-glycals generated from the corresponding pyranoses and furanoses and give trifluoromethylated compounds under mild conditions in moderate to good yields. DFT calculations have allowed a rationalization of the observed (Z)-stereoselectivity.
- Frédéric, Christophe J.-M.,Cornil, Jér?me,Vandamme, Mathilde,Dumitrescu, Lidia,Tikad, Abdellatif,Robiette, Rapha?l,Vincent, Stéphane P.
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supporting information
p. 6769 - 6773
(2018/10/24)
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- Total Synthesis of (-)-C/D-cis-Dehydro-3-O-methyl-estradiols
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A convergent synthesis of (-)-dehydro-3-O-methyl-C/D-cis-estradiol started from stereochemically defined substituted optically active 3-(2-arylethyl)-γ-butyrolactones. Regioselective bromination of the anisyl moiety, reductive ring opening of the iodolactone, and protecting-group changes led to a Weinreb amide. This then underwent an intramolecular Grignard reaction closing the B-ring to give a tetralone with defined configuration. Introduction of C-11 through an allyl Grignard addition and subsequent ring-closing metathesis gave a tetrahydro phenanthrene derivative. Oxidation of the side-chain alcohol resulted in the key aldehyde group, and a final samarium-diiodide-mediated reductive D-ring annulation resulted in the generation of the target dehydro-C/D-cis-estradiol derivatives with high stereoselectivity. Structure elucidation was carried out using NOEDS (nuclear Overhauser enhanced differential spectroscopy) analysis on the one hand, and conversion into known 3-O-methyl-13β-estradiols by double-bond hydrogenation on the other. Further efforts to use this estradiol synthetic strategy to generate more complex steroidal natural products and pharmaceutically interesting compounds are in progress.
- Kaluza, Nora M.,Schollmeyer, Dieter,Nubbemeyer, Udo
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supporting information
p. 357 - 366
(2016/02/12)
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- Improved synthesis of the C-glucuronide/glycoside of 4-hydroxybenzylretinone (4-HBR)
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Improvements in the synthesis of carbon-linked glucuronide/ glucoside conjugates of cancer chemopreventive retinoids have been achieved starting with 2,3,4,6-tetra-Obenzyl- D-glucopyranose. The revised approach demonstrates better yields, eliminates the use of an expensive, carcinogenic protecting group reagent, and avoids much painstaking chromatography. The new approach should allow synthesis of larger quantities of the agents for detailed animal and mechanistic studies.
- Cavanaugh, Kathryn R.,Narayanasamy, Sureshbabu,Walker, Joel R.,Clagett-Dame, Margaret,Curley, Robert W.
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p. 249 - 260
(2016/10/22)
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- Northern-Southern Route to Synthetic Bacteriochlorins
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A new route to bacteriochlorins via Northern-Southern (N-S) self-condensation of a dihydrodipyrrin-acetal complements a prior Eastern-Western (E-W) route. Each bacteriochlorin was prepared in five steps from an α-halopyrrole and a 2,2-dimethylpent-4-ynoic acid. The first three steps follow Jacobi's synthesis of dihydrodipyrrins: Pd-mediated coupling to form a lactone-pyrrole, Petasis reagent treatment for methenylation, and Paal-Knorr type ring closure to form the 1,2,2-trimethyl-substituted dihydrodipyrrin. Subsequent steps entail conversion of the 1-methyl group to the 1-(dimethoxymethyl) unit and acid-catalyzed self-condensation of the resulting dihydrodipyrrin-acetal. The essential differences between the N-S and E-W routes lie in (1) the location of the gem-dimethyl group (with respect to the 1-acetal unit) at the 2- versus 3-position in the dihydrodipyrrin-acetals, respectively, (2) the method of synthesis of the dihydrodipyrrins, and consequently (3) access to diverse substituted bacteriochlorins including those with substituents at the meso-positions. Ten new bacteriochlorins bearing 0-6 total aryl, alkyl, and carboethoxy substituents at the β-pyrrole and/or meso-positions have been prepared, with yields of macrocycle formation of up to 39%. Four single-crystal X-ray structures (two intermediates, two bacteriochlorins) were determined. The bacteriochlorins exhibit characteristic bacteriochlorophyll-like absorption spectra, including a Qy band in the region 713-760 nm.
- Liu, Yizhou,Lindsey, Jonathan S.
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p. 11882 - 11897
(2016/12/09)
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- Reactions of Cp2TiMe2 with ferrocene and (n5-Cp)Co(n4-C4Ph4) derived esters and amides: A new route for 1-methylvinyl and methyl ketone derived metal sandwich compounds
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Reactions of Cp2TiMe2, with the ester derivatives of organometallic sandwich compounds (n5-RC5H4)Fe(n5-C5H5) and (n5-RC5H4)Co(n4-C4Ph4) (R=ester groups) gave products having R=C(CH2)Me, instead of the expected vinyl ethers indicating conversion of the ester units by Cp2TiMe2 to methyl ketones followed by methylenation. A reaction of Cp2TiMe2 with the diester (n5-RC5H4)Co(n4-C4Ph3R)(R=C(O)OMe) also gave similar results. The study has also been successfully extended to metal sandwich derived amides, thio and seleno esters. By controlling the amount of Cp2TiMe2, the reactions were also stopped at the methyl ketone stage and the methyl ketones were isolated in good yields and characterized. The method provides an easy and direct access to convert organometallic sandwich derived esters and related compounds to 1-methylvinyl derived products.
- Singh, Jatinder,Ghosh, Sanjib,Deb, Mayukh,Elias, Anil J.
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- Total Synthesis of Gelsemoxonine through a Spirocyclopropane Isoxazolidine Ring Contraction
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Plants of the species Gelsemium have found application in traditional Asian medicine for over a thousand years. Gelsemoxonine represents a novel constituent of this plant incorporating a highly functionalized azetidine at its core. We herein report a full
- Diethelm, Stefan,Carreira, Erick M.
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supporting information
p. 6084 - 6096
(2015/05/27)
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- Chemoselective phosphination of titanacyclobutene: A convenient method for synthesis of allylphosphine derivatives
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Titanacyclobutenes reacted with chlorophosphine to afford titanoallylphosphines with high chemoselectivity, and the resulting titanoallylphosphine could be converted into functionalized allylphosphine sulfides via reactions with various electrophiles.
- Zhou, Yiqing,Chen, Chao,Yan, Xiaoyu,Xi, Chanjuan
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supporting information
p. 844 - 846
(2014/03/21)
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- Organometallic titanocene-gold compounds as potential chemotherapeutics in renal cancer. Study of their protein kinase inhibitory properties
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Early-late transition metal TiAu2 compounds [(η-C5H5)2Ti{OC(O)CH2PPh2AuCl}2] (3) and new [(η-C5H5)2Ti{OC(O)-4-C6H4PPh2
- Fernndez-Gallardo, Jacob,Elie, Benelita T.,Sulzmaier, Florian J.,Sana, Mercedes,Ramos, Joe W.,Contel, Mara
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p. 6669 - 6681
(2015/02/19)
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- A convenient one-pot synthesis of polysubstituted pyrroles from N-protected succinimides
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The dienamine products formed by the reaction between polysubstituted succinimides and the Petasis reagent were subjected to isomerization under mild acidic conditions to give polysubstituted pyrroles in excellent yields (85-95%). The scope and limitations of this methodology are explored.
- Kobeissi, Marwan,Yazbeck, Ogaritte,Chreim, Yamama
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supporting information
p. 2523 - 2526
(2014/05/06)
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- ARYLPIPERAZINES
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The present invention relates to arylpiperazines, and to the efficient treatment of an individual afflicted with L-DOPA-induced dyskinesia, which condition typically arises as a consequence of long-term treatment with L-DOPA therapy in Parkinson patients,
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Paragraph 00165-00167
(2014/12/09)
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- Total synthesis of (±)-gelsemoxonine
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Gelsemoxonine (1) is a Gelsemium alkaloid incorporating an unusual azetidine. Its total synthesis was achieved employing a novel ring contraction of a spirocyclopropane isoxazolidine to furnish a β-lactam intermediate. This β-lactam ring was further elabo
- Diethelm, Stefan,Carreira, Erick M.
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supporting information
p. 8500 - 8503
(2013/07/19)
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- HYDANTOIN DERIVATIVES USEFUL AS KV3 INHIBITORS
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The invention provides compounds of formula (I): Said compounds being inhibitors of Kv3 channels and of use in the prophylaxis or treatment of related disorders.
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Paragraph 0878-0880
(2013/10/22)
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- Bromination of enamines from tertiary amides using the petasis reagent: A convenient one-pot regioselective route to bromomethyl ketones
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An original one-pot synthesis of bromomethyl ketones is achived using the Petasis reagent (dimethyltitanocene) as a key for enamine generation. Several amides were used to test the limits of the procedure by changing either the alkyl chain R or the amino portion of the starting materials. The enamines generated in situ were allowed to react with bromine at low temperature followed by hydrolysis to yield bromomethyl ketones in excellent yields (85 to 95%). Mechanistic details and optimum conditions for the reaction are briefly discussed. The present approach offers several advantages such as regioselectivity in enamine formation, good yields, mild reaction conditions, and ease of experimentation.
- Kobeissi, Marwan,Cherry, Khalil,Jomaa, Wissam
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supporting information
p. 2955 - 2965
(2013/09/02)
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- HYDANTOIN DERIVATIVES USEFUL AS KV3 INHIBITORS
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The invention provides compounds of formula (I): Said compounds being inhibitors of Kv3 channels and of use in the prophylaxis or treatment of related disorders.
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Page/Page column 130-131
(2012/06/30)
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- Synthesis and properties of [Cp2Ti(Me)(H2O)][B(C 6F5)4]
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Treatment of water-stable Cp2TiMe2 with [Ph 3C][B(C6F5)4] in CD 2Cl2 gives the solvent-separated ion pair [Cp 2Ti(Me)(CD2Cl2)][B(C6F 5)4], which reacts rapidly with water at 205 K to give the corresponding aqua complex [Cp2Ti(Me)(H2O)][B(C 6F5)4]. The latter has been characterized by 1H and 13C NMR spectroscopy at 205 K and is a rare, possibly unique, example of a complex containing aqua and methyl ligands within the coordination sphere of a titanium(IV) complex.
- Dunlop-Briere, Alexandre F.,Baird, Michael C.
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p. 6117 - 6120
(2011/01/03)
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- NOVEL COMPOUNDS
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Disclosed are imidazo[1,2-a]pyridin-2-ylmethyl substituted piperidine derivatives of formula (I) and their use as pharmaceuticals.
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Page/Page column 11
(2009/02/11)
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- IMIDAZO [1, 2-C] PYRIMIDIN-2-YLMETHYLPIPERIDINES AS OREXIN RECEPTOR ANTAGONISTS
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This invention relates to imidazo[1,2-c]pyrimidin-2-ylmethyl substituted piperidine derivatives and their use as pharmaceuticals.
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Page/Page column 17-18
(2009/03/07)
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- PROCESS FOR PURIFICATION OF APREPITANT
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The present invention relates to a process for obtaining pure aprepitant substantially free of undesired diastereomeric isomer, namely 5-[2(S)-[1(RS)-[3,5-bis(trifluoromethyl)-phenyl)ethoxy]-3-(S)-(4-fluorophenyl)-morpholin-4-yl-methyl]-3,4-dihydro-2H-1,2
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Page/Page column 3
(2009/06/27)
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- AN IMPROVED PROCESS FOR THE PREPARATION OF APREPITANT
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The present invention relates to an improved process for the preparation of Aprepitant of formula (I) and its intermediates. More particularly the present invention relates to the preparation of 3-(-S)-(4-fluorophenyl)-4-benzyl-2-morpholinone of Formula (III) or its salts thereof by reacting N-benzyl-(S)-(4-fluorophenyl) glycine of formula (II) with 1,2 dibromoethane in presence of an organic base.
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Page/Page column 11-12
(2009/03/07)
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- PROCESS FOR PURIFICATION OF APREPITANT
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The present invention relates to a process for obtaining pure aprepitant substantially free of undesired diastereomeric isomer, namely 5-[2(S)-[I (RS)- [3,5-bis(trifluoromethyl)-phenyl)ethoxy]-3-(S)-(4-fluorophenyl)-morpholin-4-yl- methyl]-3,4-dihydro-2H-1,2,4-triazol-3-one. The present invention further provides an improved process for preparation aprepitant crystalline form II. The present invention also relates to novel amorphous form of aprepitant, process for its preparation and to a pharmaceutical composition comprising it. The present invention further relates to aprepitant having mean particle size of less than about 11.5 microns, process for its preparation and to a pharmaceutical composition comprising it. Thus, for example, aprepitant having the content of diastereomeric impurity of 1.1 % is dissolved in ethyl acetate at 700C, the solution is concentrated to half the initial volume by distilling off ethyl acetate, and the resulting solid is collected at 0 - 50C to give pure aprepitant substantially free of diastereomeric impurity.
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Page/Page column 8
(2008/06/13)
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- A-[(E)-2-(5,6,7,8-TETRAHYDRO-5,5,8,8-TETRAMETHYL-2-NAPTHALENYL)-1-PROPENYL]BENZOIC ACID ANALOGS AND METHOD OF MANUFACTURE AND AND USE THEREOF
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Analogs of 4-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-napthalenyl)-1 - propenyl]benzoic acid and methods of manufacture and use thereof, such as for use in cancer prevention and treatment.
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Page/Page column 17
(2008/06/13)
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- C-linked glucuronide of N-(4-hydroxybenzyl) retinone, analogs thereof, and method of using the same to inhibit neoplastic cell growth
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Compounds of the formula: are described, along with pharmaceutical compositions containing these compounds, and methods of using the compounds to prevent and to treat cancer in mammals, including humans.
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Page/Page column 9-10
(2008/06/13)
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- Recycling titanocene dichloride from the petasis methylenation reaction
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A simple method for recycling the titanium species used in the Petasis methylenation reaction is described. Treatment of the titanocene oxide byproduct with chlorotrimethylsilane and pyridine allows regeneration, recovery, and successful reuse of titanocene dichloride in amounts corresponding to nearly 90% of the dimethyltitanocene reagent initially employed.
- Berget, Patrick E.,Schore, Neil E.
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p. 552 - 553
(2008/10/09)
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- Dimethyltitanocene: From millimole to kilomole
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The process development of a dimethyltitanocene-mediated ester olefination is described. The synthetic challenges and stability issues involving large-scale production of dimethyltitanocene are documented, and the optimization of the ester olefination is detailed. The process described was used to make hundreds of kilograms of an advanced intermediate for aprepitant (Emend).
- Payack, Joseph F.,Huffman, Mark A.,Cai, Dongwei,Hughes, David L.,Collins, Paul C.,Johnson, Brian K.,Cottrell, Ian F.,Tuma, Linda D.
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p. 256 - 259
(2013/09/04)
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- Regioselectivity of metallacycle formation via intramolecular CH activation
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Carbometalation of alkynes by dimethyltitanocene affords vinyl complexes which serve as intermediates for the formation of titanacyclic products through subsequent hydrogen abstraction/methane elimination. Although multiple sites for hydrogen abstraction
- Doxsee, Kenneth M,Juliette, Jerrick J.J
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p. 879 - 890
(2008/10/08)
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- Process for the synthesis of monomethylmetallocenes and dimethylmetallocenes and their solutions specifically for use in the polymerization of olefins
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Disclosed is a process for preparing methyltransition metal compounds in which the halide metallocene precursor to be alkylated is initially charged in a hydrocarbon desired for the subsequent application, admixed with an aluminum alkyl and subsequently converted by addition of an inorganic salt into the end product: STR1 The reaction solution thus obtained can be freed of precipitated salts by simple filtration and directly used for polymerization, since the dialkylmetallocene is obtained in high purity and yield. If desired, it can also be isolated without problems.
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- INFRARED SPECTRA AND METHYL GROUP PROPERTIES IN DICYCLOPENTADIENYLDIMETHYL-TITATIUM(IV), -ZIRCONIUM(IV) AND -HAFNIUM(IV)
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Infrared spectra are reported for CH3-, CD3-, and CHD2-substituted Cp2MMe2 (Cp = η5-C5H5, M = Ti, Zr, Hf) in CCl4 solution.The isolated CH stretching frequencies, ν(isCH), measured in the CHD2 species are lower than any previously observed in methylmetal compounds and the methyl CH bonds in Cp2HfMe2 are predicted to be the longest and weakest such bonds yet to have been characterised by this method.The methyl groups in Cp2ZrMe2 and Cp2HfMe2 have all three CH bonds equal, but in Cp2TiMe2 each methyl group contains two strong CH bonds and one weak one.This may be the result of steric overcrowding effects around the relatively small titanium atom.The symmetric deformation δs(CH3) rises with increasing atomic number of the metal atom, the reverse of the trend observed for methyl derivatives of Main Group elements.
- McQuillan, G. P.,McKean, D. C.,Torto, I.
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p. 183 - 196
(2007/10/02)
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- ON THE NATURE AND REACTIVITY OF Cp2TiCH3
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Reaction of Cp2TiCl with 1 eq. of CH3Li in ether at -78 deg C yields the green, thermally unstable, trivalent Ti compound Cp2TiCH3 * EPR studies on ether solutions of this compound reveal it to be present in solution as the adduct Cp2TiCH3 * OEt2 * By reaction with DCl Cp2TiCl2 and CH3D are formed.Reaction with 2,6 xylylisocyanide leads to insertion of the isocyanide into the Ti-CH3 bond, while reaction with CS2 yields the disproportionation products Cp2-Ti(CH3)2 and Cp2TiCS2.Thermal decomposition studies on deuteriated analogues confirm the Ti-CH3 structure.The ratedetermining step in the decomposition process is the abstraction of a Cp proton by the methyl group.Under nitrogen the decomposition reaction yields NH3 and N2H4 in amounts of up to 0.28 moles N/Ti.Some catalytic applications of Cp2TiCH3 for hydrogenation and isomerisation of olefins and acetylenes are briefly mentioned.
- Klei, E.,Teuben, J. H.
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