- Regioselective C-H chlorination: Towards the sequential difunctionalization of phenol derivatives and late-stage chlorination of bioactive compounds
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We have developed a protocol for the auxillary directed C-H chlorination of phenol derivatives using catalytic amounts of palladium acetate that is amenable to the late-stage chlorination of diflufenican and estrone. The 2-pyridine group allows for a highly efficient palladium-catalyzed chlorination and sequential ortho C-H functionalization reaction of phenol derivatives to produce a variety of symmetrical and unsymmetrical 2,4,6-trisubstituted phenols.
- Gao, Chao,Li, Hongchen,Liu, Miaochang,Ding, Jinchang,Huang, Xiaobo,Wu, Huayue,Gao, Wenxia,Wu, Ge
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p. 46636 - 46643
(2017/10/16)
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- Cu-Mn spinel oxide catalyzed regioselective halogenation of phenols and N-heteroarenes
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A novel simple, mild chemo- and regioselective method has been developed for the halogenation of phenols using Cu-Mn spinel oxide as a catalyst and N-halosuccinimide as halogenating agent. In the presence of Cu-Mn spinel oxide B, both electron-withdrawing and electron-donating groups bearing phenols gave monohalogenated products in good to excellent yields with highest para-selectivity. The para-substituted phenol gave monohalogenated product with good yield and ortho-selectivity. N-Heteroarenes such as indoles and imidazoles also gave monohalogenated products with high selectivity. Unlike the copper-catalyzed halogenation, the present method works well with electron-withdrawing group bearing phenols and gives comparatively better yields and selectivity. The Cu-Mn spinel catalyst is robust and reused three times under optimized conditions without any loss in catalytic activity. Nonphenolics did not undergo this transformation.
- Singh, Parvinder Pal,Thatikonda, Thanusha,Kumar, K. A. Aravinda,Sawant, Sanghapal D.,Singh, Baldev,Sharma, Amit Kumar,Sharma,Singh, Deepika,Vishwakarma, Ram A.
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experimental part
p. 5823 - 5828
(2012/09/05)
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- A practical synthesis of renin inhibitor MK-1597 (ACT-178882) via catalytic enantioselective hydrogenation and epimerization of piperidine intermediate
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A practical enantioselective synthesis of renin inhibitor MK-1597 (ACT-178882), a potential new treatment for hypertension, is described. The synthetic route provided MK-1597 in nine steps and 29% overall yield from commercially available p-cresol (7). The key features of this sequence include a catalytic asymmetric hydrogenation of a tetrasubstituted ene-ester, a highly efficient epimerization/saponification sequence of 4 which sets both stereocenters of the molecule, and a short synthesis of amine fragment 2.
- Molinaro, Carmela,Shultz, Scott,Roy, Amélie,Lau, Stephen,Trinh, Thao,Angelaud, Rémy,O'Shea, Paul D.,Abele, Stefan,Cameron, Mark,Corley, Ed,Funel, Jacques-Alexis,Steinhuebel, Dietrich,Weisel, Mark,Krska, Shane
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supporting information; experimental part
p. 1062 - 1071
(2011/04/22)
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- PROCESS FOR MAKING A RENIN INHIBITOR
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A salt of the compound (3'R,4'S)-6-[2-(2,6-Dichloro-4-methyl-phenoxy)-ethoxy]-1',2',3',4',5',6'-hexahydro-[3,4']bipyridinyl-3'-carboxylic acid [2-chloro-5-(2-methoxy-ethyl)-benzyl]-cyclopropyl-amide selected from the group consisting of monoacetate salt and bis-D-tartrate salt. In one embodiment of the invention, the salt is (3',4'S)-6-[2-(2,6-Dichloro-4-methyl-phenoxy)-ethoxy]-1',2',3',4',5',6'-hexahydro-[3,4']bipyridinyl-3'-carboxylic acid [2-chloro-5-(2-methoxy-ethyl)-benzyl]-cyclopropyl-amide monoacetate. In one embodiment of the invention, the salt is (3'R, 4'S)-6-[2-(2,6-Dichloro-4-methyl-phenoxy)-ethoxy]-1',2',3',4',5',6'-hexahydro-[3,4']bipyridinyl-3'-carboxylic acid [2-chloro-5-(2-methoxy-ethyl)-benzyl]-cyclopropyl-amide bis-D-tartrate. The invention also describes a asymmetric synthesis of (3'R, 4'S)-6-[2-(2,6-Dichloro-4-methyl-phenoxy)-ethoxy]-1',2',3',4',5',6'-hexahydro-[3,4']bipyridinyl-3'-carboxylic acid [2-chloro-5-(2-methoxy-ethyl)-benzyl]-cyclopropyl-amide as a monoacetate salt or as a bis-D-tartrate salt
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Page/Page column 10
(2010/04/03)
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- A PROCESS FOR PREPARING DIAZABICYCLO[3.3.1] NONANE COMPOUNDS
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The invention is a process for preparing a diazabicyclo compound of formula (I) process for preparing a diazabicyclo compound of formula (I):where X is selected from the group consisting of hydrogen, C1-C6 alkoxycarbonyl, and carbobenzyloxy; R6 is selected from the group consisting of C1-C6 alkyl, C2-C6 alkenyl, and benzyl; and R9, R 10, and R11 are independently selected from the group consisting of hydrogen, halogen, and C1-C6 alkyl. wherein the process involves cyclizing I-I, formula (II).
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Page/Page column 17; 37
(2008/12/07)
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- NOVEL PHARMACEUTICAL COMPOSITIONS
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The invention provides the use of compounds of formula (I) or pharmaceutically acceptable esters, amides, solvates or salts thereof, including salts of such esters or amides, and solvates of such esters, amides or salts, for the manufacture of a medicament for the treatment or prophylaxis of a condition that may be treated with a thyroid receptor agonist or partial agonist wherein R1, R2, R3, R4, Y, W and R5 are as defined in the specification. The invention also provides compounds of formula (Ia) or pharmaceutically acceptable esters, amides, solvates or salts thereof, including salts of such esters or amides, and solvates of such esters, amides or salts, formula (Ia) wherein R1, R2, R3, R4, Y, W and R5 are as defined in the specification.
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Page/Page column 47-49
(2008/06/13)
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- Highly Selective Aromatic Chlorinations. Part 2. The Chlorination of Substituted Phenols, Anisoles, Anilines, and Related Compounds with N-Chloroamines in Acidic Solution
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Phenols, anisoles, anilines, and related compounds are chlorinated in trifluoroacetic acid at room temperature by N-chlorodialkylamines and N-chlorotrialkylammonium salts.With monsubstituted compounds and their 2- and 3-substituted derivatives the reaction occurs efficiently and selectively at the 4-position.The reactivity of these substrates and the selectivity of their chlorinations are determined by electronic rather than steric effects of the substituent.Blocking the reaction with a substituent at the 4-position generally leads to only poor or moderate yields of the 2-chlorinated product.Evidence for radical and cation radical intermediates has been obtained in the reactions of some of the 4-substituted reactants and the mechanism of chlorination is discussed in the light of these findings.The reactions of selected substrates have been scaled up to give laboratory syntheses.
- Smith, John R. Lindsay,McKeer, Linda C.,Taylor, Jonathan M.
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p. 385 - 392
(2007/10/02)
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- Electrophilic Chlorination of 4-Methylphenols with Molecular Chlorine. Synthesis of Dimethoxy Aromatics by Methanolysis of 4-Chloro-4-methylcyclcohexa-2,5-dienones
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The chlorination of p-cresol (1a), 2,4-dimethylphenol (1b), 3,4-dimethylphenol (1c), 2,4,5-trimethylphenol (1d), 2,4,6-trimethylphenol (1e) and the various possible mono- and dichloro derivatives of these phenols (3a-d, 6a and 6 c) with molecular chlorine was investigated in dichloromethane or dimethyl formamide solution.The 2,6-substituted p-cresol derivatives all give quantitative yields of 4-chloro-4-methylcyclohexa-2,5-dienones (5b, 5d, 7a, 7c and 2e), whereas the less substituted p-cresol derivatives give a 20-25percent yield of corresponding 4-chloro-4-methylcyclohexa-2,5-dienones (2a-d, 5a and 5c), the other products being chlorinated phenols.Treatment of 4-chloro-4-methylcyclohexa-2,5-dienones with at least one of the double bonds of the ring unsubstituted (2a-c and 4a) with methanol gave a quantitative yield of a 1,3-dimethoxybenzene derivative (9a-c and 10), whereas similar treatment of 4-chloro-2,4,5-trimethylcyclohexa-2,5-dienone (2d) gave 5-methoxy-2,3-dimethylbenzyl methyl ether (11).Treatment of the other 4-chlorodienones with methanol gave the corresponding 4-methoxydienones.Electrophilic chlorination of certain p-cresol derivatives followed by methanolysis hence is a facile although low-yield method for 3-methoxylation or selective side chain oxidation of these p-cresol derivatives.
- Bergquist, Karl-Erik,Nilsson, Anders,Ronlan, Alvin
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p. 675 - 684
(2007/10/02)
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